Biopolym. Cell. 2024; 40(1):14-36.
http://dx.doi.org/10.7124/bc.000AAA
Огляди
Генетичні та епігенетичні порушення у раках людини
1Геращенко Г. В., 1Кашуба В. І., 1Тукало М. А.
  1. Інститут молекулярної біології і генетики НАН України
    Вул. Академіка Заболотного, 150, Київ, Україна, 03143

Abstract

У процесі канцерогенезу клітини пухлин набувають певних ракових ознак, в основі яких лежать зміни на різних молекулярних рівнях. В даному огляді розглянуто порушення у ракових клітинах на генетичному та епігенетичному рівнях. Генетичні порушення розглянуто на прикладі семи видів раків, серед яких рак легені, молочної залози, передміхурової залози, колоректальний, нирки, шийки матки та ячників. Генетичні зміни порушують функціонування як онкогенів, так і генів супресорів пухлин та спостерігаються як делеції або ампліфікації, аберації хромосом та локусів хромосом, тисячі соматичних мутацій у генах, поява онкогенних гібридних транскриптів тощо. Епігенетичні порушення також є багатоплановими. Серед них гіперметилювання та гіпометилювання промоторів генів, модифікації пістонів, зміна профілів експресії некодувальних РНК та інші. Генетичні та епігенетичні порушення мають як пухлино-специфічний характер, так і загальний, притаманний багатьом видам епітелійних пухлин. Завдяки розробці сучасних широкомасштабних методів детекції генетичних та епігенетичних порушень є змога одночасного виявлення цих порушень та молекулярного профілювання різних типів раків. Багато з цих порушень можуть бути мішенями для діагностики раку та розробки ефективних методів лікування.
Keywords: канцерогенез, гени супресори росту пухлин, онкогени, делеція, ампліфікація, втрата гетерозиготності, соматичні та зародкові мутації, метилювання промотора, некодуючі РНК, секвенування нового покоління
Повний текст: (PDF, англійською)

References

[1] Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000; 100(1):57-70.
[2] Lin L, Li Z, Yan L, Liu Y, Yang H, Li H. Global, regional, and national cancer incidence and death for 29 cancer groups in 2019 and trends analysis of the global cancer burden, 1990-2019. J Hematol Oncol. 2021; 14(1):197.
[3] Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022; 72(1):7-33.
[4] Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74.
[5] Hanahan D. Hallmarks of Cancer: New Dimensions. Cancer Discov. 2022; 12(1):31-46.
[6] Rosario SR, Long MD, Affronti HC, Rowsam AM, Eng KH, Smiraglia DJ. Pan-cancer analysis of transcriptional metabolic dysregulation using The Cancer Genome Atlas. Nat Commun. 2018; 9(1):5330.
[7] Chakraborty S, Hosen MI, Ahmed M, Shekhar HU. Onco-Multi-OMICS Approach: A New Frontier in Cancer Research. Biomed Res Int. 2018; 2018:9836256.
[8] McCombie WR, McPherson JD, Mardis ER. Next-Generation Sequencing Technologies. Cold Spring Harb Perspect Med. 2019; 9(11):a036798.
[9] Sharma S, Floren M, Ding Y, Stenmark KR, Tan W, Bryant SJ. A photoclickable peptide microarray platform for facile and rapid screening of 3-D tissue microenvironments. Biomaterials. 2017; 143:17-28.
[10] Mardis ER. The Impact of Next-Generation Sequencing on Cancer Genomics: From Discovery to Clinic. Cold Spring Harb Perspect Med. 2019; 9(9):a036269.
[11] Chakravarthi BV, Nepal S, Varambally S. Genomic and Epigenomic Alterations in Cancer. Am J Pathol. 2016; 186(7):1724-35.
[12] Ilango S, Paital B, Jayachandran P, Padma PR, Nirmaladevi R. Epigenetic alterations in cancer. Front Biosci (Landmark Ed). 2020; 25(6):1058-109.
[13] Kopinski PK, Singh LN, Zhang S, Lott MT, Wallace DC. Mitochondrial DNA variation and cancer. Nat Rev Cancer. 2021; 21(7):431-45.
[14] Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA Jr, Kinzler KW. Cancer genome landscapes. Science. 2013; 339(6127):1546-58.
[15] Iurlaro R, León-Annicchiarico CL, Muñoz-Pinedo C. Regulation of cancer metabolism by oncogenes and tumor suppressors. Methods Enzymol. 2014; 542:59-80.
[16] Siddiqui IA, Sanna V, Ahmad N, Sechi M, Mukhtar H. Resveratrol nanoformulation for cancer prevention and therapy. Ann N Y Acad Sci. 2015; 1348(1):20-31.
[17] Lee EY, Muller WJ. Oncogenes and tumor suppressor genes. Cold Spring Harb Perspect Biol. 2010; 2(10):a003236.
[18] Vogelstein B, Kinzler KW. Cancer genes and the pathways they control. Nat Med. 2004; 10(8):789-99.
[19] Xu W, Gu J, Ren Q, Shi Y, Xia Q, Wang J, Wang S, Wang Y, Wang J. NFATC1 promotes cell growth and tumorigenesis in ovarian cancer up-regulating c-Myc through ERK1/2/p38 MAPK signal pathway. Tumour Biol. 2016; 37(4):4493-500.
[20] Moghadam AR, Patrad E, Tafsiri E, Peng W, Fangman B, Pluard TJ, Accurso A, Salacz M, Shah K, Ricke B, Bi D, Kimura K, Graves L, Najad MK, Dolatkhah R, Sanaat Z, Yazdi M, Tavakolinia N, Mazani M, Amani M, Ghavami S, Gartell R, Reilly C, Naima Z, Esfandyari T, Farassati F. Ral signaling pathway in health and cancer. Cancer Med. 2017; 6(12):2998-3013.
[21] Krishnamurthy N, Kurzrock R. Targeting the Wnt/beta-catenin pathway in cancer: Update on effectors and inhibitors. Cancer Treat Rev. 2018; 62:50-60.
[22] Mabuchi S, Kuroda H, Takahashi R, Sasano T. The PI3K/AKT/mTOR pathway as a therapeutic target in ovarian cancer. Gynecol Oncol. 2015; 137(1):173-9.
[23] Creighton CJ. Multiple oncogenic pathway signatures show coordinate expression patterns in human prostate tumors. PLoS One. 2008; 3(3):e1816.
[24] Bild AH, Yao G, Chang JT, Wang Q, Potti A, Chasse D, Joshi MB, Harpole D, Lancaster JM, Berchuck A, Olson JA Jr, Marks JR, Dressman HK, West M, Nevins JR. Oncogenic pathway signatures in human cancers as a guide to targeted therapies. Nature. 2006; 439(7074):353-7.
[25] Luzzatto L. Somatic mutations in cancer development. Environ Health. 2011; 10(Suppl 1):S12.
[26] Sugimura T, Terada M, Yokota J, Hirohashi S, Wakabayashi K. Multiple genetic alterations in human carcinogenesis. Environ Health Perspect. 1992; 98:5-12.
[27] Bessarabova M, Pustovalova O, Shi W, Serebriyskaya T, Ishkin A, Polyak K, Velculescu VE, Nikolskaya T, Nikolsky Y. Functional synergies yet distinct modulators affected by genetic alterations in common human cancers. Cancer Res. 2011; 71(10):3471-81.
[28] Lundberg A, Lindström LS, Parker JS, Löverli E, Perou CM, Bergh J, Tobin NP. A pan-cancer analysis of the frequency of DNA alterations across cell cycle activity levels. Oncogene. 2020; 39(32):5430-40.
[29] Schneider G, Schmidt-Supprian M, Rad R, Saur D. Tissue-specific tumorigenesis: context matters. Nat Rev Cancer. 2017; 17(4):239-53.
[30] Gammall J, Lai AG. Pan-cancer prognostic genetic mutations and clinicopathological factors associated with survival outcomes: a systematic review. NPJ Precis Oncol. 2022; 6(1):27.
[31] Schaefer MH, Serrano L. Cell type-specific properties and environment shape tissue specificity of cancer genes. Sci Rep. 2016; 6:20707.
[32] Steele CD, Pillay N, Alexandrov LB. An overview of mutational and copy number signatures in human cancer. J Pathol. 2022; 257(4):454-65.
[33] McClelland SE. Role of chromosomal instability in cancer progression. Endocr Relat Cancer. 2017; 24(9):T23-T31.
[34] Wang WJ, Li LY, Cui JW. Chromosome structural variation in tumorigenesis: mechanisms of formation and carcinogenesis. Epigenetics Chromatin. 2020; 13(1):49.
[35] Zheng J. Oncogenic chromosomal translocations and human cancer (review). Oncol Rep. 2013; 30(5):2011-9.
[36] Canoy RJ, Shmakova A, Karpukhina A, Shepelev M, Germini D, Vassetzky Y. Factors That Affect the Formation of Chromosomal Translocations in Cells. Cancers (Basel). 2022; 14(20):5110.
[37] Ryland GL, Doyle MA, Goode D, Boyle SE, Choong DY, Rowley SM, Li J; Australian Ovarian Cancer Study Group; Bowtell DD, Tothill RW, Campbell IG, Gorringe KL. Loss of heterozygosity: what is it good for? BMC Med Genomics. 2015; 8:45.
[38] Zhang X, Sjöblom T. Targeting Loss of Heterozygosity: A Novel Paradigm for Cancer Therapy. Pharmaceuticals (Basel). 2021; 14(1):57.
[39] van den Bosch T, Derks S, Miedema DM. Chromosomal Instability, Selection and Competition: Factors That Shape the Level of Karyotype Intra-Tumor Heterogeneity. Cancers (Basel). 2022; 14(20):4986.
[40] Hoevenaar WHM, Janssen A, Quirindongo AI, Ma H, Klaasen SJ, Teixeira A, van Gerwen B, Lansu N, Morsink FHM, Offerhaus GJA, Medema RH, Kops GJPL, Jelluma N. Degree and site of chromosomal instability define its oncogenic potential. Nat Commun. 2020; 11(1):1501.
[41] Yu B, O'Toole SA, Trent RJ. Somatic DNA mutation analysis in targeted therapy of solid tumours. Transl Pediatr. 2015; 4(2):125-38.
[42] Rezaie N, Bayati M, Hamidi M, Tahaei MS, Khorasani S, Lovell NH, Breen J, Rabiee HR, Alinejad-Rokny H. Somatic point mutations are enriched in non-coding RNAs with possible regulatory function in breast cancer. Commun Biol. 2022; 5(1):556.
[43] Bailey MH, Tokheim C, Porta-Pardo E, Sengupta S, Bertrand D, Weerasinghe A, Colaprico A, Wendl MC, Kim J, Reardon B, Ng PK, Jeong KJ, Cao S, Wang Z, Gao J, Gao Q, Wang F, Liu EM, Mularoni L, Rubio-Perez C, Nagarajan N, Cortés-Ciriano I, Zhou DC, Liang WW, Hess JM, Yellapantula VD, Tamborero D, Gonzalez-Perez A, Suphavilai C, Ko JY, Khurana E, Park PJ, Van Allen EM, Liang H; MC3 Working Group; Cancer Genome Atlas Research Network; Lawrence MS, Godzik A, Lopez-Bigas N, Stuart J, Wheeler D, Getz G, Chen K, Lazar AJ, Mills GB, Karchin R, Ding L. Comprehensive Characterization of Cancer Driver Genes and Mutations. Cell. 2018; 173(2):371-85.e18.
[44] Wu L, Yao H, Chen H, Wang A, Guo K, Gou W, Yu Y, Li X, Yao M, Yuan S, Pang F, Hu J, Chen L, Liu W, Yao J, Zhang S, Dong X, Wang W, Hu J, Ling Q, Ding S, Wei Y, Li Q, Cao W, Wang S, Di Y, Feng F, Zhao G, Zhang J, Huang L, Xu J, Yan W, Tong Z, Jiang D, Ji T, Li Q, Xu L, He H, Shang L, Liu J, Wang K, Wu D, Shen J, Liu Y, Zhang T, Liang C, Wang Y, Shang Y, Guo J, Liang G, Xu S, Liu J, Wang K, Wang M. Landscape of somatic alterations in large-scale solid tumors from an Asian population. Nat Commun. 2022; 13(1):4264.
[45] Niida A, Nagayama S, Miyano S, Mimori K. Understanding intratumor heterogeneity by combining genome analysis and mathematical modeling. Cancer Sci. 2018; 109(4):884-92.
[46] Mimori K, Saito T, Niida A, Miyano S. Cancer evolution and heterogeneity. Ann Gastroenterol Surg. 2018; 2(5):332-8.
[47] Steuer CE, Behera M, Berry L, Kim S, Rossi M, Sica G, Owonikoko TK, Johnson BE, Kris MG, Bunn PA, Khuri FR, Garon EB, Ramalingam SS. Role of race in oncogenic driver prevalence and outcomes in lung adenocarcinoma: Results from the Lung Cancer Mutation Consortium. Cancer. 2016; 122(5):766-72.
[48] Varella-Garcia M. Chromosomal and genomic changes in lung cancer. Cell Adh Migr. 2010; 4(1):100-6.
[49] Hirsch FR, Varella-Garcia M, Cappuzzo F, McCoy J, Bemis L, Xavier AC, Dziadziuszko R, Gumerlock P, Chansky K, West H, Gazdar AF, Crino L, Gandara DR, Franklin WA, Bunn PA Jr. Combination of EGFR gene copy number and protein expression predicts outcome for advanced non-small-cell lung cancer patients treated with gefitinib. Ann Oncol. 2007; 18(4):752-60.
[50] Heighway J, Betticher DC. Lung tumors: an overview. Atlas Genet Cytogenet Oncol Haematol. 2004; 8(2):137-9.
[51] Micke P, Edlund K, Holmberg L, Kultima HG, Mansouri L, Ekman S, Bergqvist M, Scheibenflug L, Lamberg K, Myrdal G, Berglund A, Andersson A, Lambe M, Nyberg F, Thomas A, Isaksson A, Botling J. Gene copy number aberrations are associated with survival in histologic subgroups of non-small cell lung cancer. J Thorac Oncol. 2011; 6(11):1833-40.
[52] Baykara O, Bakir B, Buyru N, Kaynak K, Dalay N. Amplification of chromosome 8 genes in lung cancer. J Cancer. 2015; 6(3):270-5.
[53] VanderLaan PA, Rangachari D, Mockus SM, Spotlow V, Reddi HV, Malcolm J, Huberman MS, Joseph LJ, Kobayashi SS, Costa DB. Mutations in TP53, PIK3CA, PTEN and other genes in EGFR mutated lung cancers: Correlation with clinical outcomes. Lung Cancer. 2017; 106:17-21.
[54] Wang H, Zhang W, Wang K, Li X. Correlation between EML4-ALK, EGFR and clinicopathological features based on IASLC/ATS/ERS classification of lung adenocarcinoma. Medicine (Baltimore). 2018; 97(26):e11116.
[55] Sholl LM, Aisner DL, Varella-Garcia M, Berry LD, Dias-Santagata D, Wistuba II, Chen H, Fujimoto J, Kugler K, Franklin WA, Iafrate AJ, Ladanyi M, Kris MG, Johnson BE, Bunn PA, Minna JD, Kwiatkowski DJ; LCMC Investigators. Multi-institutional Oncogenic Driver Mutation Analysis in Lung Adenocarcinoma: The Lung Cancer Mutation Consortium Experience. J Thorac Oncol. 2015; 10(5):768-77.
[56] Loginov VI, Dmitriev AA, Senchenko VN, Pronina IV, Khodyrev DS, Kudryavtseva AV, Krasnov GS, Gerashchenko GV, Chashchina LI, Kazubskaya TP, Kondratieva TT, Lerman MI, Angeloni D, Braga EA, Kashuba VI. Tumor Suppressor Function of the SEMA3B Gene in Human Lung and Renal Cancers. PLoS One. 2015; 10(5):e0123369.
[57] Watkins EJ. Overview of breast cancer. JAAPA. 2019; 32(10):13-17.
[58] Davis NM, Sokolosky M, Stadelman K, Abrams SL, Libra M, Candido S, Nicoletti F, Polesel J, Maestro R, D'Assoro A, Drobot L, Rakus D, Gizak A, Laidler P, Dulińska-Litewka J, Basecke J, Mijatovic S, Maksimovic-Ivanic D, Montalto G, Cervello M, Fitzgerald TL, Demidenko Z, Martelli AM, Cocco L, Steelman LS, McCubrey JA. Deregulation of the EGFR/PI3K/PTEN/Akt/mTORC1 pathway in breast cancer: possibilities for therapeutic intervention. Oncotarget. 2014; 5(13):4603-50.
[59] Ngeow J, Sesock K, Eng C. Breast cancer risk and clinical implications for germline PTEN mutation carriers. Breast Cancer Res Treat. 2017; 165(1):1-8.
[60] Kechagioglou P, Papi RM, Provatopoulou X, Kalogera E, Papadimitriou E, Grigoropoulos P, Nonni A, Zografos G, Kyriakidis DA, Gounaris A. Tumor suppressor PTEN in breast cancer: heterozygosity, mutations and protein expression. Anticancer Res. 2014; 34(3):1387-400.
[61] Corso G, Intra M, Trentin C, Veronesi P, Galimberti V. CDH1 germline mutations and hereditary lobular breast cancer. Fam Cancer. 2016; 15(2):215-9.
[62] Vuong D, Simpson PT, Green B, Cummings MC, Lakhani SR. Molecular classification of breast cancer. Virchows Arch. 2014; 465(1):1-14.
[63] Rastelli F, Biancanelli S, Falzetta A, Martignetti A, Casi C, Bascioni R, Giustini L, Crispino S. Triple-negative breast cancer: current state of the art. Tumori. 2010; 96(6):875-88.
[64] Ahn SG, Kim SJ, Kim C, Jeong J. Molecular Classification of Triple-Negative Breast Cancer. J Breast Cancer. 2016; 19(3):223-30.
[65] Chauchereau A, Aarab-Terrisse S. Prostate tumors: an overview. Atlas Genet Cytogenet Oncol Haematol. 2011; 15(12):1067-73.
[66] Watson PA, Chen YF, Balbas MD, Wongvipat J, Socci ND, Viale A, Kim K, Sawyers CL. Constitutively active androgen receptor splice variants expressed in castration-resistant prostate cancer require full-length androgen receptor. Proc Natl Acad Sci U S A. 2010; 107(39):16759-65.
[67] Salameh A, Lee AK, Cardó-Vila M, Nunes DN, Efstathiou E, Staquicini FI, Dobroff AS, Marchiò S, Navone NM, Hosoya H, Lauer RC, Wen S, Salmeron CC, Hoang A, Newsham I, Lima LA, Carraro DM, Oliviero S, Kolonin MG, Sidman RL, Do KA, Troncoso P, Logothetis CJ, Brentani RR, Calin GA, Cavenee WK, Dias-Neto E, Pasqualini R, Arap W. PRUNE2 is a human prostate cancer suppressor regulated by the intronic long noncoding RNA PCA3. Proc Natl Acad Sci U S A. 2015; 112(27):8403-8.
[68] Gasi Tandefelt D, Boormans J, Hermans K, Trapman J. ETS fusion genes in prostate cancer. Endocr Relat Cancer. 2014; 21(3):R143-52.
[69] Fontana F, Anselmi M, Limonta P. Molecular mechanisms and genetic alterations in prostate cancer: From diagnosis to targeted therapy. Cancer Lett. 2022; 534:215619.
[70] Schumacher FR, Basourakos SP, Lewicki PJ, Vince R, Spratt DE, Barbieri CE, Shoag JE. Race and Genetic Alterations in Prostate Cancer. JCO Precis Oncol. 2021; 5:PO.21.00324.
[71] Gerashchenko GV, Mevs LV, Chashchina LI, Pikul MV, Gryzodub OP, Stakhovsky EO, Kashuba VI. Expression of steroid and peptide hormone receptors, metabolic enzymes and EMT-related genes in prostate tumors in relation to the presence of the TMPRSS2/ERG fusion. Exp Oncol. 2018; 40(2):101-8.
[72] Koelzer VH, Dawson H, Zlobec I, Lugli A. Colon: Colorectal adenocarcinoma. Atlas Genet Cytogenet Oncol Haematol. 2013; 17(5):348-63.
[73] Mármol I, Sánchez-de-Diego C, Pradilla Dieste A, Cerrada E, Rodriguez Yoldi MJ. Colorectal Carcinoma: A General Overview and Future Perspectives in Colorectal Cancer. Int J Mol Sci. 2017; 18(1):197.
[74] Kirzin S, Marisa L, Guimbaud R, De Reynies A, Legrain M, Laurent-Puig P, Cordelier P, Pradère B, Bonnet D, Meggetto F, Portier G, Brousset P, Selves J. Sporadic early-onset colorectal cancer is a specific sub-type of cancer: a morphological, molecular and genetics study. PLoS One. 2014; 9(8):e103159.
[75] Cuyle PJ, Prenen H. Current and future biomarkers in the treatment of colorectal cancer. Acta Clin Belg. 2017; 72(2):103-15.
[76] Day FL, Jorissen RN, Lipton L, Mouradov D, Sakthianandeswaren A, Christie M, Li S, Tsui C, Tie J, Desai J, Xu ZZ, Molloy P, Whitehall V, Leggett BA, Jones IT, McLaughlin S, Ward RL, Hawkins NJ, Ruszkiewicz AR, Moore J, Busam D, Zhao Q, Strausberg RL, Gibbs P, Sieber OM. PIK3CA and PTEN gene and exon mutation-specific clinicopathologic and molecular associations in colorectal cancer. Clin Cancer Res. 2013; 19(12):3285-96.
[77] Hechtman JF, Sadowska J, Huse JT, Borsu L, Yaeger R, Shia J, Vakiani E, Ladanyi M, Arcila ME. AKT1 E17K in Colorectal Carcinoma Is Associated with BRAF V600E but Not MSI-H Status: A Clinicopathologic Comparison to PIK3CA Helical and Kinase Domain Mutants. Mol Cancer Res. 2015; 13(6):1003-8.
[78] Linehan WM. Genetic basis of kidney cancer: role of genomics for the development of disease-based therapeutics. Genome Res. 2012; 22(11):2089-100.
[79] Kim BJ, Kim JH, Kim HS, Zang DY. Prognostic and predictive value of VHL gene alteration in renal cell carcinoma: a meta-analysis and review. Oncotarget. 2017; 8(8):13979-85.
[80] Sanchez DJ, Simon MC. Genetic and metabolic hallmarks of clear cell renal cell carcinoma. Biochim Biophys Acta Rev Cancer. 2018; 1870(1):23-31.
[81] Schödel J, Grampp S, Maher ER, Moch H, Ratcliffe PJ, Russo P, Mole DR. Hypoxia, Hypoxia-inducible Transcription Factors, and Renal Cancer. Eur Urol. 2016; 69(4):646-57.
[82] Senchenko VN, Kisseljova NP, Ivanova TA, Dmitriev AA, Krasnov GS, Kudryavtseva AV, Panasenko GV, Tsitrin EB, Lerman MI, Kisseljov FL, Kashuba VI, Zabarovsky ER. Novel tumor suppressor candidates on chromosome 3 revealed by NotI-microarrays in cervical cancer. Epigenetics. 2013; 8(4):409-20.
[83] Atkin NB. Significance of chromosome 5 and 17 changes in the development of carcinoma of the cervix uteri. Cytogenet Cell Genet. 2000; 91(1-4):44-6.
[84] Kersemaekers AM, Kenter GG, Hermans J, Fleuren GJ, van de Vijver MJ. Allelic loss and prognosis in carcinoma of the uterine cervix. Int J Cancer. 1998; 79(4):411-7.
[85] Mitra AB. Genetic deletion and human papillomavirus infection in cervical cancer: loss of heterozygosity sites at 3p and 5p are important genetic events. Int J Cancer. 1999; 82(3):322-4.
[86] Femi OF. Genetic alterations and PIK3CA gene mutations and amplifications analysis in cervical cancer by racial groups in the United States. Int J Health Sci (Qassim). 2018; 12(1):28-32.
[87] Cardoso MFS, Castelletti CHM, Lima-Filho JL, Martins DBG, Teixeira JAC. Putative biomarkers for cervical cancer: SNVs, methylation and expression profiles. Mutat Res Rev Mutat Res. 2017; 773:161-73.
[88] Wijetunga NA, Belbin TJ, Burk RD, Whitney K, Abadi M, Greally JM, Einstein MH, Schlecht NF. Novel epigenetic changes in CDKN2A are associated with progression of cervical intraepithelial neoplasia. Gynecol Oncol. 2016; 142(3):566-73.
[89] Naseem A, Bhat ZI, Kalaiarasan P, Kumar B, Gandhi G, Rizvi MMA. Genetic and epigenetic alterations affecting PARK-2 expression in cervical neoplasm among North Indian patients. Tumour Biol. 2017; 39(6):1010428317703635.
[90] Aunoble B, Sanches R, Didier E, Bignon YJ. Major oncogenes and tumor suppressor genes involved in epithelial ovarian cancer (review). Int J Oncol. 2000; 16(3):567-76.
[91] Shibuya Y, Tokunaga H, Saito S, Shimokawa K, Katsuoka F, Bin L, Kojima K, Nagasaki M, Yamamoto M, Yaegashi N, Yasuda J. Identification of somatic genetic alterations in ovarian clear cell carcinoma with next generation sequencing. Genes Chromosomes Cancer. 2018; 57(2):51-60.
[92] Vanderstichele A, Busschaert P, Olbrecht S, Lambrechts D, Vergote I. Genomic signatures as predictive biomarkers of homologous recombination deficiency in ovarian cancer. Eur J Cancer. 2017; 86:5-14.
[93] Leung DTH, Fuller PJ, Chu S. Impact of FOXL2 mutations on signaling in ovarian granulosa cell tumors. Int J Biochem Cell Biol. 2016; 72:51-4.
[94] Anttonen M, Pihlajoki M, Andersson N, Georges A, L'hôte D, Vattulainen S, Färkkilä A, Unkila-Kallio L, Veitia RA, Heikinheimo M. FOXL2, GATA4, and SMAD3 co-operatively modulate gene expression, cell viability and apoptosis in ovarian granulosa cell tumor cells. PLoS One. 2014; 9(1):e85545.
[95] Bubancova I, Kovarikova H, Laco J, Ruszova E, Dvorak O, Palicka V, Chmelarova M. Next-Generation Sequencing Approach in Methylation Analysis of HNF1B and GATA4 Genes: Searching for Biomarkers in Ovarian Cancer. Int J Mol Sci. 2017; 18(2):474.
[96] Shah S, Cheung A, Kutka M, Sheriff M, Boussios S. Epithelial Ovarian Cancer: Providing Evidence of Predisposition Genes. Int J Environ Res Public Health. 2022; 19(13):8113.
[97] Gerashchenko GV, Gordiyuk VV, Kashuba VI. Genetic and epigenetic alterations of human chromosome 3, investigated by NotI-microarrays in seven types of epithelial cancers. Biopolym Cell. 2018; 34(4):303-12.
[98] Dmitriev AA, Rosenberg EE, Krasnov GS, Gerashchenko GV, Gordiyuk VV, Pavlova TV, Kudryavtseva AV, Beniaminov AD, Belova AA, Bondarenko YN, Danilets RO, Glukhov AI, Kondratov AG, Alexeyenko A, Alekseev BY, Klein G, Senchenko VN, Kashuba VI. Identification of Novel Epigenetic Markers of Prostate Cancer by NotI-Microarray Analysis. Dis Markers. 2015; 2015:241301.
[99] Rudenko EE, Gerashchenko GV, Lapska YV, Bogatyrova OO, Vozianov SO, Zgonnyk YM, Kashuba VI. Genetic and epigenetic changes of GPX1 and GPX3 in human clear-cell renal cell carcinoma. Biopolym Cell. 2013; 29(5):395-401.
[100] Gerashchenko GV, Bogatyrova OO, Rudenko EE, Kondratov AG, Gordiyuk VV, Zgonnyk YM, Vozianov OF, Pavlova TV, Zabarovsky ER, Rynditch AV, Kashuba VI. Genetic and epigenetic changes of NKIRAS1 gene in human renal cell carcinomas. Exp Oncol. 2010; 32(2):71-5.
[101] Poulos RC, Wong YT, Ryan R, Pang H, Wong JWH. Analysis of 7,815 cancer exomes reveals associations between mutational processes and somatic driver mutations. PLoS Genet. 2018; 14(11):e1007779.
[102] Rübben A, Araujo A. Cancer heterogeneity: converting a limitation into a source of biologic information. J Transl Med. 2017; 15(1):190.
[103] Ryu D, Joung JG, Kim NK, Kim KT, Park WY. Deciphering intratumor heterogeneity using cancer genome analysis. Hum Genet. 2016; 135(6):635-42.
[104] Merid SK, Goranskaya D, Alexeyenko A. Distinguishing between driver and passenger mutations in individual cancer genomes by network enrichment analysis. BMC Bioinformatics. 2014; 15(1):308.
[105] McFarland CD, Yaglom JA, Wojtkowiak JW, Scott JG, Morse DL, Sherman MY, Mirny LA. The Damaging Effect of Passenger Mutations on Cancer Progression. Cancer Res. 2017; 77(18):4763-72.
[106] Gomez K, Miura S, Huuki LA, Spell BS, Townsend JP, Kumar S. Somatic evolutionary timings of driver mutations. BMC Cancer. 2018; 18(1):85.
[107] Song J, Peng W, Wang F. An Entropy-Based Method for Identifying Mutual Exclusive Driver Genes in Cancer. IEEE/ACM Trans Comput Biol Bioinform. 2020; 17(3):758-68.
[108] Hou Y, Gao B, Li G, Su Z. MaxMIF: A New Method for Identifying Cancer Driver Genes through Effective Data Integration. Adv Sci (Weinh). 2018; 5(9):1800640.
[109] Bii VM, Trobridge GD. Identifying Cancer Driver Genes Using Replication-Incompetent Retroviral Vectors. Cancers (Basel). 2016; 8(11):99.
[110] Bii VM, Collins CP, Hocum JD, Trobridge GD. Replication-incompetent gammaretroviral and lentiviral vector-based insertional mutagenesis screens identify prostate cancer progression genes. Oncotarget. 2018; 9(21):15451-63.
[111] Poon SL, McPherson JR, Tan P, Teh BT, Rozen SG. Mutation signatures of carcinogen exposure: genome-wide detection and new opportunities for cancer prevention. Genome Med. 2014; 6(3):24.
[112] Phillips DH. Mutational spectra and mutational signatures: Insights into cancer aetiology and mechanisms of DNA damage and repair. DNA Repair (Amst). 2018; 71:6-11.
[113] Harris RS. Cancer mutation signatures, DNA damage mechanisms, and potential clinical implications. Genome Med. 2013; 5(9):87.
[114] Perduca V, Omichessan H, Baglietto L, Severi G. Mutational and epigenetic signatures in cancer tissue linked to environmental exposures and lifestyle. Curr Opin Oncol. 2018; 30(1):61-7.
[115] Salter JD, Bennett RP, Smith HC. The APOBEC Protein Family: United by Structure, Divergent in Function. Trends Biochem Sci. 2016; 41(7):578-94.
[116] Adolph MB, Love RP, Feng Y, Chelico L. Enzyme cycling contributes to efficient induction of genome mutagenesis by the cytidine deaminase APOBEC3B. Nucleic Acids Res. 2017; 45(20):11925-40.
[117] Shi K, Carpenter MA, Banerjee S, Shaban NM, Kurahashi K, Salamango DJ, McCann JL, Starrett GJ, Duffy JV, Demir Ö, Amaro RE, Harki DA, Harris RS, Aihara H. Structural basis for targeted DNA cytosine deamination and mutagenesis by APOBEC3A and APOBEC3B. Nat Struct Mol Biol. 2017; 24(2):131-9.
[118] Tate JG, Bamford S, Jubb HC, Sondka Z, Beare DM, Bindal N, Boutselakis H, Cole CG, Creatore C, Dawson E, Fish P, Harsha B, Hathaway C, Jupe SC, Kok CY, Noble K, Ponting L, Ramshaw CC, Rye CE, Speedy HE, Stefancsik R, Thompson SL, Wang S, Ward S, Campbell PJ, Forbes SA. COSMIC: the Catalogue Of Somatic Mutations In Cancer. Nucleic Acids Res. 2019; 47(D1):D941-D7.
[119] Castro-Muñoz LJ, Ulloa EV, Sahlgren C, Lizano M, De La Cruz-Hernández E, Contreras-Paredes A. Modulating epigenetic modifications for cancer therapy (Review). Oncol Rep. 2023; 49(3):59.
[120] Madkour MM, Ramadan WS, Saleh E, El-Awady R. Epigenetic modulations in cancer: predictive biomarkers and potential targets for overcoming the resistance to topoisomerase I inhibitors. Ann Med. 2023; 55(1):2203946.
[121] Miranda Furtado CL, Dos Santos Luciano MC, Silva Santos RD, Furtado GP, Moraes MO, Pessoa C. Epidrugs: targeting epigenetic marks in cancer treatment. Epigenetics. 2019; 14(12):1164-76.
[122] Ehrlich M. DNA hypomethylation in cancer cells. Epigenomics. 2009; 1(2):239-59.
[123] Hatziapostolou M, Iliopoulos D. Epigenetic aberrations during oncogenesis. Cell Mol Life Sci. 2011; 68(10):1681-702.
[124] Robertson KD, Jones PA. DNA methylation: past, present and future directions. Carcinogenesis. 2000; 21(3):461-7.
[125] Ren W, Gao L, Song J. Structural Basis of DNMT1 and DNMT3A-Mediated DNA Methylation. Genes (Basel). 2018; 9(12):620.
[126] Walton EL, Francastel C, Velasco G. Maintenance of DNA methylation: Dnmt3b joins the dance. Epigenetics. 2011; 6(11):1373-7.
[127] Jeltsch A, Jurkowska RZ. New concepts in DNA methylation. Trends Biochem Sci. 2014; 39(7):310-8.
[128] Wade PA. Methyl CpG-binding proteins and transcriptional repression. Bioessays. 2001; 23(12):1131-7.
[129] Du Q, Luu PL, Stirzaker C, Clark SJ. Methyl-CpG-binding domain proteins: readers of the epigenome. Epigenomics. 2015; 7(6):1051-73.
[130] Chen YC, Gotea V, Margolin G, Elnitski L. Significant associations between driver gene mutations and DNA methylation alterations across many cancer types. PLoS Comput Biol. 2017; 13(11):e1005840.
[131] Saghafinia S, Mina M, Riggi N, Hanahan D, Ciriello G. Pan-Cancer Landscape of Aberrant DNA Methylation across Human Tumors. Cell Rep. 2018; 25(4):1066-80.e8.
[132] Spainhour JC, Lim HS, Yi SV, Qiu P. Correlation Patterns Between DNA Methylation and Gene Expression in The Cancer Genome Atlas. Cancer Inform. 2019; 18:1176935119828776.
[133] Hughes LA, Khalid-de Bakker CA, Smits KM, van den Brandt PA, Jonkers D, Ahuja N, Herman JG, Weijenberg MP, van Engeland M. The CpG island methylator phenotype in colorectal cancer: progress and problems. Biochim Biophys Acta. 2012; 1825(1):77-85.
[134] Hughes LA, Melotte V, de Schrijver J, de Maat M, Smit VT, Bovée JV, French PJ, van den Brandt PA, Schouten LJ, de Meyer T, van Criekinge W, Ahuja N, Herman JG, Weijenberg MP, van Engeland M. The CpG island methylator phenotype: what's in a name? Cancer Res. 2013; 73(19):5858-68.
[135] Fang F, Turcan S, Rimner A, Kaufman A, Giri D, Morris LG, Shen R, Seshan V, Mo Q, Heguy A, Baylin SB, Ahuja N, Viale A, Massague J, Norton L, Vahdat LT, Moynahan ME, Chan TA. Breast cancer methylomes establish an epigenomic foundation for metastasis. Sci Transl Med. 2011; 3(75):75ra25.
[136] Oue N, Oshimo Y, Nakayama H, Ito R, Yoshida K, Matsusaki K, Yasui W. DNA methylation of multiple genes in gastric carcinoma: association with histological type and CpG island methylator phenotype. Cancer Sci. 2003; 94(10):901-5.
[137] Noushmehr H, Weisenberger DJ, Diefes K, Phillips HS, Pujara K, Berman BP, Pan F, Pelloski CE, Sulman EP, Bhat KP, Verhaak RG, Hoadley KA, Hayes DN, Perou CM, Schmidt HK, Ding L, Wilson RK, Van Den Berg D, Shen H, Bengtsson H, Neuvial P, Cope LM, Buckley J, Herman JG, Baylin SB, Laird PW, Aldape K; Cancer Genome Atlas Research Network. Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell. 2010; 17(5):510-22.
[138] Arai E, Chiku S, Mori T, Gotoh M, Nakagawa T, Fujimoto H, Kanai Y. Single-CpG-resolution methylome analysis identifies clinicopathologically aggressive CpG island methylator phenotype clear cell renal cell carcinomas. Carcinogenesis. 2012; 33(8):1487-93.
[139] Tanemura A, Terando AM, Sim MS, van Hoesel AQ, de Maat MF, Morton DL, Hoon DS. CpG island methylator phenotype predicts progression of malignant melanoma. Clin Cancer Res. 2009; 15(5):1801-7.
[140] Suzuki H, Yamamoto E, Maruyama R, Niinuma T, Kai M. Biological significance of the CpG island methylator phenotype. Biochem Biophys Res Commun. 2014; 455(1-2):35-42.
[141] Teodoridis JM, Hardie C, Brown R. CpG island methylator phenotype (CIMP) in cancer: causes and implications. Cancer Lett. 2008; 268(2):177-86.
[142] Biswas S, Rao CM. Epigenetics in cancer: Fundamentals and Beyond. Pharmacol Ther. 2017; 173:118-34.
[143] Ramakrishnan V. Histone structure and the organization of the nucleosome. Annu Rev Biophys Biomol Struct. 1997; 26:83-112.
[144] Jenuwein T, Allis CD. Translating the histone code. Science. 2001; 293(5532):1074-80.
[145] du Preez LL, Patterton HG. The effect of epigenetic modifications on the secondary structures and possible binding positions of the N-terminal tail of histone H3 in the nucleosome: a computational study. J Mol Model. 2017; 23(4):137.
[146] Strahl BD, Allis CD. The language of covalent histone modifications. Nature. 2000; 403(6765):41-5.
[147] Audia JE, Campbell RM. Histone Modifications and Cancer. Cold Spring Harb Perspect Biol. 2016; 8(4):a019521.
[148] Wang R, Xin M, Li Y, Zhang P, Zhang M. The Functions of Histone Modification Enzymes in Cancer. Curr Protein Pept Sci. 2016; 17(5):438-45.
[149] Shin DG, Bayarsaihan D. A Novel Epi-drug Therapy Based on the Suppression of BET Family Epigenetic Readers. Yale J Biol Med. 2017; 90(1):63-71.
[150] Mio C, Bulotta S, Russo D, Damante G. Reading Cancer: Chromatin Readers as Druggable Targets for Cancer Treatment. Cancers (Basel). 2019; 11(1):61.
[151] Ellis L, Atadja PW, Johnstone RW. Epigenetics in cancer: targeting chromatin modifications. Mol Cancer Ther. 2009; 8(6):1409-20.
[152] Xu WS, Parmigiani RB, Marks PA. Histone deacetylase inhibitors: molecular mechanisms of action. Oncogene. 2007; 26(37):5541-52.
[153] Negmeldin AT, Knoff JR, Pflum MKH. The structural requirements of histone deacetylase inhibitors: C4-modified SAHA analogs display dual HDAC6/HDAC8 selectivity. Eur J Med Chem. 2018; 143:1790-806.
[154] Farani MR, Sarlak M, Gholami A, Azaraian M, Binabaj MM, Kakavandi S, Tambuwala MM, Taheriazam A, Hashemi M, Ghasemi S. Epigenetic drugs as new emerging therapeutics: What is the scale's orientation of application and challenges? Pathol Res Pract. 2023; 248:154688.
[155] Miranda-Gonçalves V, Lameirinhas A, Henrique R, Jerónimo C. Metabolism and Epigenetic Interplay in Cancer: Regulation and Putative Therapeutic Targets. Front Genet. 2018; 9:427.
[156] Santosh B, Varshney A, Yadava PK. Non-coding RNAs: biological functions and applications. Cell Biochem Funct. 2015; 33(1):14-22.
[157] Kaikkonen MU, Lam MT, Glass CK. Non-coding RNAs as regulators of gene expression and epigenetics. Cardiovasc Res. 2011; 90(3):430-40.
[158] Nahkuri S, Paro R. The role of noncoding RNAs in chromatin regulation during differentiation. Wiley Interdiscip Rev Dev Biol. 2012; 1(5):743-52.
[159] Chen J, Xue Y. Emerging roles of non-coding RNAs in epigenetic regulation. Sci China Life Sci. 2016; 59(3):227-35.
[160] Klinge CM. Non-Coding RNAs in Breast Cancer: Intracellular and Intercellular Communication. Noncoding RNA. 2018; 4(4):40.
[161] Vallone C, Rigon G, Gulia C, Baffa A, Votino R, Morosetti G, Zaami S, Briganti V, Catania F, Gaffi M, Nucciotti R, Costantini FM, Piergentili R, Putignani L, Signore F. Non-Coding RNAs and Endometrial Cancer. Genes (Basel). 2018; 9(4):187.
[162] Grillone K, Riillo C, Scionti F, Rocca R, Tradigo G, Guzzi PH, Alcaro S, Di Martino MT, Tagliaferri P, Tassone P. Non-coding RNAs in cancer: platforms and strategies for investigating the genomic "dark matter". J Exp Clin Cancer Res. 2020; 39(1):117.
[163] Yang M, Lu H, Liu J, Wu S, Kim P, Zhou X. lncRNAfunc: a knowledgebase of lncRNA function in human cancer. Nucleic Acids Res. 2022; 50(D1):D1295-D306.
[164] Yamamura S, Imai-Sumida M, Tanaka Y, Dahiya R. Interaction and cross-talk between non-coding RNAs. Cell Mol Life Sci. 2018; 75(3):467-84.
[165] Esteller M. Non-coding RNAs in human disease. Nat Rev Genet. 2011; 12(12):861-74.
[166] Singh NK. miRNAs target databases: developmental methods and target identification techniques with functional annotations. Cell Mol Life Sci. 2017; 74(12):2239-61.
[167] Anastasiadou E, Jacob LS, Slack FJ. Non-coding RNA networks in cancer. Nat Rev Cancer. 2018; 18(1):5-18.
[168] Forrest ME, Khalil AM. Review: Regulation of the cancer epigenome by long non-coding RNAs. Cancer Lett. 2017; 407:106-12.
[169] Kondo Y, Shinjo K, Katsushima K. Long non-coding RNAs as an epigenetic regulator in human cancers. Cancer Sci. 2017; 108(10):1927-33.
[170] Zhou Z, Lin Z, Pang X, Tariq MA, Ao X, Li P, Wang J. Epigenetic regulation of long non-coding RNAs in gastric cancer. Oncotarget. 2017; 9(27):19443-58.
[171] Carrer A, Wellen KE. Metabolism and epigenetics: a link cancer cells exploit. Curr Opin Biotechnol. 2015; 34:23-9.
[172] Montellier E, Gaucher J. Targeting the interplay between metabolism and epigenetics in cancer. Curr Opin Oncol. 2019; 31(2):92-9.
[173] Tran TQ, Lowman XH, Kong M. Molecular Pathways: Metabolic Control of Histone Methylation and Gene Expression in Cancer. Clin Cancer Res. 2017; 23(15):4004-9.
[174] McCullough LE, Chen J, Cho YH, Khankari NK, Bradshaw PT, White AJ, Teitelbaum SL, Terry MB, Neugut AI, Hibshoosh H, Santella RM, Gammon MD. Modification of the association between recreational physical activity and survival after breast cancer by promoter methylation in breast cancer-related genes. Breast Cancer Res. 2017; 19(1):19.
[175] Liu Y, Tian S, Ning B, Huang T, Li Y, Wei Y. Stress and cancer: The mechanisms of immune dysregulation and management. Front Immunol. 2022; 13:1032294.
[176] Weinstein IB, Joe A. Oncogene addiction. Cancer Res. 2008; 68(9):3077-80; discussion 3080.
[177] Bellovin DI, Das B, Felsher DW. Tumor dormancy, oncogene addiction, cellular senescence, and self-renewal programs. Adv Exp Med Biol. 2013; 734:91-107.
[178] Shen J, Li L, Yang T, Cheng N, Sun G. Drug Sensitivity Screening and Targeted Pathway Analysis Reveal a Multi-Driver Proliferative Mechanism and Suggest a Strategy of Combination Targeted Therapy for Colorectal Cancer Cells. Molecules. 2019; 24(3):623.
[179] Casey SC, Li Y, Felsher DW. An essential role for the immune system in the mechanism of tumor regression following targeted oncogene inactivation. Immunol Res. 2014; 58(2-3):282-91.
[180] Koutsimpelas D, Pongsapich W, Heinrich U, Mann S, Mann WJ, Brieger J. Promoter methylation of MGMT, MLH1 and RASSF1A tumor suppressor genes in head and neck squamous cell carcinoma: pharmacological genome demethylation reduces proliferation of head and neck squamous carcinoma cells. Oncol Rep. 2012; 27(4):1135-41.
[181] Fukushige S, Kondo E, Horii A. Methyl-CpG targeted transcriptional activation allows re-expression of tumor suppressor genes in human cancer cells. Biochem Biophys Res Commun. 2008; 377(2):600-5.
[182] Lin HY, Kuo YC, Weng YI, Lai IL, Huang TH, Lin SP, Niu DM, Chen CS. Activation of silenced tumor suppressor genes in prostate cancer cells by a novel energy restriction-mimetic agent. Prostate. 2012; 72(16):1767-78.
[183] Gupta A, Shah K, Oza MJ, Behl T. Reactivation of p53 gene by MDM2 inhibitors: A novel therapy for cancer treatment. Biomed Pharmacother. 2019; 109:484-92.
[184] Kazanets A, Shorstova T, Hilmi K, Marques M, Witcher M. Epigenetic silencing of tumor suppressor genes: Paradigms, puzzles, and potential. Biochim Biophys Acta. 2016; 1865(2):275-88.
[185] Mayr LM, Bojanic D. Novel trends in high-throughput screening. Curr Opin Pharmacol. 2009; 9(5):580-8.
[186] Wang Y, Cheng T, Bryant SH. PubChem BioAssay: A Decade's Development toward Open High-Throughput Screening Data Sharing. SLAS Discov. 2017; 22(6):655-66.
[187] Rhodes DR, Yu J, Shanker K, Deshpande N, Varambally R, Ghosh D, Barrette T, Pandey A, Chinnaiyan AM. ONCOMINE: a cancer microarray database and integrated data-mining platform. Neoplasia. 2004; 6(1):1-6.
[188] Li DY, Chen WJ, Luo L, Wang YK, Shang J, Zhang Y, Chen G, Li SK. Prospective lncRNA-miRNA-mRNA regulatory network of long non-coding RNA LINC00968 in non-small cell lung cancer A549 cells: A miRNA microarray and bioinformatics investigation. Int J Mol Med. 2017; 40(6):1895-906.
[189] Gu W, Sun Y, Zheng X, Ma J, Hu XY, Gao T, Hu MJ. Identification of Gastric Cancer-Related Circular RNA through Microarray Analysis and Bioinformatics Analysis. Biomed Res Int. 2018; 2018:2381680.
[190] Müller S, Raulefs S, Bruns P, Afonso-Grunz F, Plötner A, Thermann R, Jäger C, Schlitter AM, Kong B, Regel I, Roth WK, Rotter B, Hoffmeier K, Kahl G, Koch I, Theis FJ, Kleeff J, Winter P, Michalski CW. Next-generation sequencing reveals novel differentially regulated mRNAs, lncRNAs, miRNAs, sdRNAs and a piRNA in pancreatic cancer. Mol Cancer. 2015; 14:94.
[191] Shull AY, Noonepalle SK, Lee EJ, Choi JH, Shi H. Sequencing the cancer methylome. Methods Mol Biol. 2015; 1238:627-51.
[192] Vogtmann E, Goedert JJ. Epidemiologic studies of the human microbiome and cancer. Br J Cancer. 2016; 114(3):237-42.
[193] Mullish BH, Osborne LS, Marchesi JR, McDonald JA. The implementation of omics technologies in cancer microbiome research. Ecancermedicalscience. 2018; 12:864.
[194] Sinclair I, Stearns R, Pringle S, Wingfield J, Datwani S, Hall E, Ghislain L, Majlof L, Bachman M. Novel Acoustic Loading of a Mass Spectrometer: Toward Next-Generation High-Throughput MS Screening. J Lab Autom. 2016; 21(1):19-26.
[195] Le Gallo M, Lozy F, Bell DW. Next-Generation Sequencing. Adv Exp Med Biol. 2017; 943:119-48.
[196] Chang YS, Huang HD, Yeh KT, Chang JG. Identification of novel mutations in endometrial cancer patients by whole-exome sequencing. Int J Oncol. 2017; 50(5):1778-84.
[197] Besaratinia A, Li H, Yoon JI, Zheng A, Gao H, Tommasi S. A high-throughput next-generation sequencing-based method for detecting the mutational fingerprint of carcinogens. Nucleic Acids Res. 2012; 40(15):e116.
[198] Maslov AY, Quispe-Tintaya W, Gorbacheva T, White RR, Vijg J. High-throughput sequencing in mutation detection: A new generation of genotoxicity tests? Mutat Res. 2015; 776:136-43.
[199] Wakai T, Prasoon P, Hirose Y, Shimada Y, Ichikawa H, Nagahashi M. Next-generation sequencing-based clinical sequencing: toward precision medicine in solid tumors. Int J Clin Oncol. 2019; 24(2):115-22.
[200] Takeuchi S, Okuda S. Knowledge base toward understanding actionable alterations and realizing precision oncology. Int J Clin Oncol. 2019; 24(2):123-30.
[201] Luthra R, Patel KP, Routbort MJ, Broaddus RR, Yau J, Simien C, Chen W, Hatfield DZ, Medeiros LJ, Singh RR. A Targeted High-Throughput Next-Generation Sequencing Panel for Clinical Screening of Mutations, Gene Amplifications, and Fusions in Solid Tumors. J Mol Diagn. 2017; 19(2):255-64.
[202] Nagahashi M, Shimada Y, Ichikawa H, Kameyama H, Takabe K, Okuda S, Wakai T. Next generation sequencing-based gene panel tests for the management of solid tumors. Cancer Sci. 2019; 110(1):6-15.
[203] Morash M, Mitchell H, Beltran H, Elemento O, Pathak J. The Role of Next-Generation Sequencing in Precision Medicine: A Review of Outcomes in Oncology. J Pers Med. 2018; 8(3):30.
[204] Siu LL, Conley BA, Boerner S, LoRusso PM. Next-Generation Sequencing to Guide Clinical Trials. Clin Cancer Res. 2015; 21(20):4536-44.
[205] Groisberg R, Hong DS, Roszik J, Janku F, Tsimberidou AM, Javle M, Meric-Bernstam F, Subbiah V. Clinical Next-Generation Sequencing for Precision Oncology in Rare Cancers. Mol Cancer Ther. 2018; 17(7):1595-601.
[206] Morganti S, Tarantino P, Ferraro E, D'Amico P, Viale G, Trapani D, Duso BA, Curigliano G. Complexity of genome sequencing and reporting: Next generation sequencing (NGS) technologies and implementation of precision medicine in real life. Crit Rev Oncol Hematol. 2019; 133:171-82.
[207] Sengupta S, Sun SQ, Huang KL, Oh C, Bailey MH, Varghese R, Wyczalkowski MA, Ning J, Tripathi P, McMichael JF, Johnson KJ, Kandoth C, Welch J, Ma C, Wendl MC, Payne SH, Fenyö D, Townsend RR, Dipersio JF, Chen F, Ding L. Integrative omics analyses broaden treatment targets in human cancer. Genome Med. 2018; 10(1):60.
[208] Yu KH, Snyder M. Omics Profiling in Precision Oncology. Mol Cell Proteomics. 2016; 15(8):2525-36.
[209] Tebani A, Afonso C, Marret S, Bekri S. Omics-Based Strategies in Precision Medicine: Toward a Paradigm Shift in Inborn Errors of Metabolism Investigations. Int J Mol Sci. 2016; 17(9):1555.
[210] Ding MQ, Chen L, Cooper GF, Young JD, Lu X. Precision Oncology beyond Targeted Therapy: Combining Omics Data with Machine Learning Matches the Majority of Cancer Cells to Effective Therapeutics. Mol Cancer Res. 2018; 16(2):269-78.
[211] Piñeiro-Yáñez E, Reboiro-Jato M, Gómez-López G, Perales-Patón J, Troulé K, Rodríguez JM, Tejero H, Shimamura T, López-Casas PP, Carretero J, Valencia A, Hidalgo M, Glez-Peña D, Al-Shahrour F. PanDrugs: a novel method to prioritize anticancer drug treatments according to individual genomic data. Genome Med. 2018; 10(1):41.
[212] Verma R, Sharma PC. Next generation sequencing-based emerging trends in molecular biology of gastric cancer. Am J Cancer Res. 2018; 8(2):207-25.