Intratumoral heterogeneity in a minority of ovarian low-grade serous carcinomas

BMC Cancer

Volumn 14, Issue 1, 2014, Pages

  Tone, Alicia A ^a,b,c   McConechy, Melissa K ^a,b   Yang, Winnie ^b   Ding, Jiarui ^a   Yip, Stephen ^a,b   Kong, Esther ^b   Wong, Kwong Kwok ^d   Gershenson, David M ^d   Mackay, Helen ^c   Shah, Sohrab ^a   Gilks, Blake ^a   Tinker, Anna V ^b   Clarke, Blaise ^e   McAlpine, Jessica N ^a,b   Huntsman, David ^a,b  

^a UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^b BRITISH COLUMBIA CANCER AGENCY   (Canada)

^c PRINCESS MARGARET HOSPITAL   (Canada)

^d UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^e UNIVERSITY OF TORONTO   (Canada)

Author keywords

BRAF; Heterogeneity; KRAS; Low grade cancer; Mutation; NRAS; Ovarian serous carcinoma; SMAD4

Indexed keywords

B RAF KINASE; DNA; K RAS PROTEIN; SMAD4 PROTEIN; BRAF PROTEIN, HUMAN; GUANOSINE TRIPHOSPHATASE; KRAS PROTEIN, HUMAN; MEMBRANE PROTEIN; NRAS PROTEIN, HUMAN; ONCOPROTEIN; RAS PROTEIN;

ADULT; AGED; ARTICLE; BRAF GENE; CANCER STAGING; CELL HETEROGENEITY; CLINICAL ARTICLE; CONTROLLED STUDY; DNA ISOLATION; FEMALE; GENE MUTATION; GENE SEQUENCE; GENETIC STABILITY; HUMAN; MIDDLE AGED; MINORITY GROUP; MUTATIONAL ANALYSIS; ONCOGENE; ONCOGENE K RAS; ONCOGENE N RAS; OVARIAN LOW GRADE SEROUS CARCINOMA; OVARY CARCINOMA; POLYMERASE CHAIN REACTION; PRIMARY TUMOR; SOMATIC MUTATION; TUMOR RECURRENCE; CYSTADENOCARCINOMA; DNA MUTATIONAL ANALYSIS; GENETIC HETEROGENEITY; GENETICS; MUTATION; OVARY TUMOR; PATHOLOGY;

ADULT; CYSTADENOCARCINOMA, SEROUS; DNA MUTATIONAL ANALYSIS; FEMALE; GENETIC HETEROGENEITY; GTP PHOSPHOHYDROLASES; HUMANS; MEMBRANE PROTEINS; MIDDLE AGED; MUTATION; OVARIAN NEOPLASMS; PROTO-ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS B-RAF; RAS PROTEINS;

EID: 84924415609     PISSN: None     EISSN: 14712407     Source Type: Journal    
DOI: 10.1186/1471-2407-14-982     Document Type: Article

References (64)

1. Gershenson DM, Sun CC, Lu KH, Coleman RL, Sood AK, Malpica A, Deavers MT, Silva EG, Bodurka DC: Clinical behavior of stage II-IV low-grade serous carcinoma of the ovary. Obstet Gynecol 2006,108(2):361-368. 10.1097/01.AOG.0000227787.24587.d1
2. Schmeler KM, Gershenson DM: Low-grade serous ovarian cancer: a unique disease. Curr Oncol Rep 2008,10(6):519-523. 10.1007/s11912-008-0078-8
3. Diaz-Padilla I, Malpica AL, Minig L, Chiva LM, Gershenson DM, Gonzalez-Martin A: Ovarian low-grade serous carcinoma: a comprehensive update. Gynecol Oncol 2012,126(2):279-285. 10.1016/j.ygyno.2012.04.029
4. Bodurka DC, Deavers MT, Tian C, Sun CC, Malpica A, Coleman RL, Lu KH, Sood AK, Birrer MJ, Ozols R, Baergen R, Emerson RE, Steinhoff M, Behmaram B, Rasty G, Gershenson DM: Reclassification of serous ovarian carcinoma by a 2-tier system: a gynecologic oncology group study. Cancer 2012,118(12):3087-3094. 10.1002/cncr.26618
5. Malpica A, Deavers MT, Lu K, Bodurka DC, Atkinson EN, Gershenson DM, Silva EG: Grading ovarian serous carcinoma using a two-tier system. Am J Surg Pathol 2004,28(4):496-504. 10.1097/00000478-200404000-00009
6. Vang R, Shih Ie M, Kurman RJ: Ovarian low-grade and high-grade serous carcinoma: pathogenesis, clinicopathologic and molecular biologic features, and diagnostic problems. Adv Anat Pathol 2009,16(5):267-282. 10.1097/PAP.0b013e3181b4fffa
7. Schmeler KM, Sun CC, Bodurka DC, Deavers MT, Malpica A, Coleman RL, Ramirez PT, Gershenson DM: Neoadjuvant chemotherapy for low-grade serous carcinoma of the ovary or peritoneum. Gynecol Oncol 2008,108(3):510-514. 10.1016/j.ygyno.2007.11.013
8. Gershenson DM, Sun CC, Bodurka D, Coleman RL, Lu KH, Sood AK, Deavers M, Malpica AL, Kavanagh JJ: Recurrent low-grade serous ovarian carcinoma is relatively chemoresistant. Gynecol Oncol 2009,114(1):48-52. 10.1016/j.ygyno.2009.03.001
9. Fader AN, Java J, Ueda S, Bristow RE, Armstrong DK, Bookman MA, Gershenson DM: Survival in women with grade 1 serous ovarian carcinoma. Obstet Gynecol 2013,122(2 Pt 1):225-232.
10. Jones S, Wang TL, Kurman RJ, Nakayama K, Velculescu VE, Vogelstein B, Kinzler KW, Papadopoulos N, Shih Ie M: Low-grade serous carcinomas of the ovary contain very few point mutations. J Pathol 2012,226(3):413-420. 10.1002/path.3967
11. Singer G, Oldt R III, Cohen Y, Wang BG, Sidransky D, Kurman RJ, Shih Ie M: Mutations in BRAF and KRAS characterize the development of low-grade ovarian serous carcinoma. J Natl Cancer Inst 2003,95(6):484-486. 10.1093/jnci/95.6.484
12. Wong KK, Tsang YT, Deavers MT, Mok SC, Zu Z, Sun C, Malpica A, Wolf JK, Lu KH, Gershenson DM: BRAF mutation is rare in advanced-stage low-grade ovarian serous carcinomas. Am J Pathol 2010,177(4):1611-1617. 10.2353/ajpath.2010.100212
13. Grisham RN, Iyer G, Garg K, DeLair D, Hyman DM, Zhou Q, Iasonos A, Berger MF, Dao F, Spriggs DR, Levine DA, Aghajanian C, Solit DB: BRAF mutation is associated with early stage disease and improved outcome in patients with low-grade serous ovarian cancer. Cancer 2013,119(3):548-554. 10.1002/cncr.27782
14. Romero I, Sun CC, Wong KK, Bast RC Jr, Gershenson DM: Low-grade serous carcinoma: new concepts and emerging therapies. Gynecol Oncol 2013,130(3):660-666. 10.1016/j.ygyno.2013.05.021
15. Staebler A, Heselmeyer-Haddad K, Bell K, Riopel M, Perlman E, Ried T, Kurman RJ: Micropapillary serous carcinoma of the ovary has distinct patterns of chromosomal imbalances by comparative genomic hybridization compared with atypical proliferative serous tumors and serous carcinomas. Hum Pathol 2002,33(1):47-59. 10.1053/hupa.2002.30212
16. Crispens MA, Bodurka D, Deavers M, Lu K, Silva EG, Gershenson DM: Response and survival in patients with progressive or recurrent serous ovarian tumors of low malignant potential. Obstet Gynecol 2002,99(1):3-10. 10.1016/S0029-7844(01)01649-0
17. Ho CL, Kurman RJ, Dehari R, Wang TL, Shih IM: Mutations of BRAF and KRAS precede the development of ovarian serous borderline tumors. Cancer Res 2004,64(19):6915-6918. 10.1158/0008-5472.CAN-04-2067
18. Farley J, Brady WE, Vathipadiekal V, Lankes HA, Coleman R, Morgan MA, Mannel R, Yamada SD, Mutch D, Rodgers WH, Birrer M, Gershenson DM: Selumetinib in women with recurrent low-grade serous carcinoma of the ovary or peritoneum: an open-label, single-arm, phase 2 study. Lancet Oncol 2013,14(2):134-140. 10.1016/S1470-2045(12)70572-7
19. Nakayama N, Nakayama K, Yeasmin S, Ishibashi M, Katagiri A, Iida K, Fukumoto M, Miyazaki K: KRAS or BRAF mutation status is a useful predictor of sensitivity to MEK inhibition in ovarian cancer. Br J Cancer 2008,99(12):2020-2028. 10.1038/sj.bjc.6604783
20. Allen LF, Sebolt-Leopold J, Meyer MB: CI-1040 (PD184352), a targeted signal transduction inhibitor of MEK (MAPKK). Semin Oncol 2003,30(5 Suppl 16):105-116.
21. Pohl G, Ho CL, Kurman RJ, Bristow R, Wang TL, Shih IM: Inactivation of the mitogen-activated protein kinase pathway as a potential target-based therapy in ovarian serous tumors with KRAS or BRAF mutations. Cancer Res 2005,65(5):1994-2000. 10.1158/0008-5472.CAN-04-3625
22. Rothberg JM, Hinz W, Rearick TM, Schultz J, Mileski W, Davey M, Leamon JH, Johnson K, Milgrew MJ, Edwards M, Hoon J, Simons JF, Marran D, Myers JW, Davidson JF, Branting A, Nobile JR, Puc BP, Light D, Clark TA, Huber M, Branciforte JT, Stoner IB, Cawley SE, Lyons M, Fu Y, Homer N, Sedova M, Miao X, Reed B, et al.: An integrated semiconductor device enabling non-optical genome sequencing. Nature 2011,475(7356):348-352. 10.1038/nature10242
23. Li H, Durbin R: Fast and accurate long-read alignment with Burrows-Wheeler transform. Bioinformatics 2010,26(5):589-595. 10.1093/bioinformatics/btp698
24. Ding J, Bashashati A, Roth A, Oloumi A, Tse K, Zeng T, Haffari G, Hirst M, Marra MA, Condon A, Aparicio S, Shah SP: Feature-based classifiers for somatic mutation detection in tumour-normal paired sequencing data. Bioinformatics 2012,28(2):167-175. 10.1093/bioinformatics/btr629
25. Reva B, Antipin Y, Sander C: Predicting the functional impact of protein mutations: application to cancer genomics. Nucleic Acids Res 2011,39(17):e118. 10.1093/nar/gkr407
26. Li H: Aligning Sequence Reads, Clone Sequences and Assembly Contigs with bwa-mem. arXiv Preprint arXiv. 2013, 1303.
27. McConechy MK, Anglesio MS, Kalloger SE, Yang W, Senz J, Chow C, Heravi-Moussavi A, Morin GB, Mes-Masson AM, Carey MS, McAlpine JN, Kwon JS, Prentice LM, Boyd N, Shah SP, Gilks CB, Huntsman DG: Subtype-specific mutation of PPP2R1A in endometrial and ovarian carcinomas. J Pathol 2011,223(5):567-573. 10.1002/path.2848
28. Geisler J: Differences between the non-steroidal aromatase inhibitors anastrozole and letrozole-of clinical importance? Br J Cancer 2011,104(7):1059-1066. 10.1038/bjc.2011.58
29. Cancer Genome Atlas Research Network: Integrated genomic analyses of ovarian carcinoma. Nature 2011,474(7353):609-615. 10.1038/nature10166
30. Jones S, Wang TL, Shih Ie M, Mao TL, Nakayama K, Roden R, Glas R, Slamon D, Diaz LA Jr, Vogelstein B, Kinzler KW, Velculescu VE, Papadopoulos N: Frequent mutations of chromatin remodeling gene ARID1A in ovarian clear cell carcinoma. Science 2010,330(6001):228-231. 10.1126/science.1196333
31. Dhomen N, Reis-Filho JS, da Rocha Dias S, Hayward R, Savage K, Delmas V, Larue L, Pritchard C, Marais R: Oncogenic Braf induces melanocyte senescence and melanoma in mice. Cancer Cell 2009,15(4):294-303. 10.1016/j.ccr.2009.02.022
32. Wajapeyee N, Serra RW, Zhu X, Mahalingam M, Green MR: Oncogenic BRAF induces senescence and apoptosis through pathways mediated by the secreted protein IGFBP7. Cell 2008,132(3):363-374. 10.1016/j.cell.2007.12.032
33. Zeppernick F, Ardighieri L, Hannibal CG, Vang R, Junge J, Kjaer SK, Zhang R, Kurman RJ, Shih IM: BRAF mutation is associated with a specific cell type with features suggestive of senescence in ovarian serous borderline (Atypical Proliferative) tumors. Am J Surg Pathol. 2014,38(12):1603-1611. 10.1097/PAS.0000000000000313
34. Iacobuzio-Donahue CA, Song J, Parmiagiani G, Yeo CJ, Hruban RH, Kern SE: Missense mutations of MADH4: characterization of the mutational hot spot and functional consequences in human tumors. Clin Cancer Res 2004,10(5):1597-1604. 10.1158/1078-0432.CCR-1121-3
35. Lassus H, Salovaara R, Aaltonen LA, Butzow R: Allelic analysis of serous ovarian carcinoma reveals two putative tumor suppressor loci at 18q22-q23 distal to SMAD4, SMAD2, and DCC. Am J Pathol 2001,159(1):35-42. 10.1016/S0002-9440(10)61670-7
36. Sameer AS, Chowdri NA, Syeed N, Banday MZ, Shah ZA, Siddiqi MA: SMAD4-molecular gladiator of the TGF-beta signaling is trampled upon by mutational insufficiency in colorectal carcinoma of Kashmiri population: an analysis with relation to KRAS proto-oncogene. BMC Cancer. 2010, 10:300. 10.1186/1471-2407-10-300
37. Bardeesy N, Cheng KH, Berger JH, Chu GC, Pahler J, Olson P, Hezel AF, Horner J, Lauwers GY, Hanahan D, DePinho RA: Smad4 is dispensable for normal pancreas development yet critical in progression and tumor biology of pancreas cancer. Genes Dev 2006,20(22):3130-3146. 10.1101/gad.1478706
38. Vakiani E, Solit DB: KRAS and BRAF: drug targets and predictive biomarkers. J Pathol 2011,223(2):219-229.
39. Miller VA, Riely GJ, Zakowski MF, Li AR, Patel JD, Heelan RT, Kris MG, Sandler AB, Carbone DP, Tsao A, Herbst RS, Heller G, Ladanyi M, Pao W, Johnson DH: Molecular characteristics of bronchioloalveolar carcinoma and adenocarcinoma, bronchioloalveolar carcinoma subtype, predict response to erlotinib. J Clin Oncol 2008,26(9):1472-1478. 10.1200/JCO.2007.13.0062
40. Pao W, Wang TY, Riely GJ, Miller VA, Pan Q, Ladanyi M, Zakowski MF, Heelan RT, Kris MG, Varmus HE: KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med 2005,2(1):e17. 10.1371/journal.pmed.0020017
41. Zhu CQ, da Cunha Santos G, Ding K, Sakurada A, Cutz JC, Liu N, Zhang T, Marrano P, Whitehead M, Squire JA, Kamel-Reid S, Seymour L, Shepherd FA, Tsao MS: Role of KRAS and EGFR as biomarkers of response to Erlotinib in national cancer institute of Canada clinical trials group study BR.21. J Clin Oncol 2008,26(26):4268-4275. 10.1200/JCO.2007.14.8924
42. 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):752-760.
43. Eberhard DA, Johnson BE, Amler LC, Goddard AD, Heldens SL, Herbst RS, Ince WL, Janne PA, Januario T, Johnson DH, Klein P, Miller VA, Ostland MA, Ramies DA, Sebisanovic D, Stinson JA, Zhang YR, Seshagiri S, Hillan KJ: Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib. J Clin Oncol 2005,23(25):5900-5909. 10.1200/JCO.2005.02.857
44. Janakiraman M, Vakiani E, Zeng Z, Pratilas CA, Taylor BS, Chitale D, Halilovic E, Wilson M, Huberman K, Ricarte Filho JC, Persaud Y, Levine DA, Fagin JA, Jhanwar SC, Mariadason JM, Lash A, Ladanyi M, Saltz LB, Heguy A, Paty PB, Solit DB: Genomic and biological characterization of exon 4 KRAS mutations in human cancer. Cancer Res 2010,70(14):5901-5911. 10.1158/0008-5472.CAN-10-0192
45. De Roock W, Claes B, Bernasconi D, De Schutter J, Biesmans B, Fountzilas G, Kalogeras KT, Kotoula V, Papamichael D, Laurent-Puig P, Penault-Llorca F, Rougier P, Vincenzi B, Santini D, Tonini G, Cappuzzo F, Frattini M, Molinari F, Saletti P, De Dosso S, Martini M, Bardelli A, Siena S, Sartore-Bianchi A, Tabernero J, Macarulla T, Di Fiore F, Gangloff AO, Ciardiello F, Pfeiffer P, et al.: Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol 2010,11(8):753-762. 10.1016/S1470-2045(10)70130-3
46. Loupakis F, Ruzzo A, Cremolini C, Vincenzi B, Salvatore L, Santini D, Masi G, Stasi I, Canestrari E, Rulli E, Floriani I, Bencardino K, Galluccio N, Catalano V, Tonini G, Magnani M, Fontanini G, Basolo F, Falcone A, Graziano F: KRAS codon 61, 146 and BRAF mutations predict resistance to cetuximab plus irinotecan in KRAS codon 12 and 13 wild-type metastatic colorectal cancer. Br J Cancer 2009,101(4):715-721. 10.1038/sj.bjc.6605177
47. Herman JM, Fan KY, Wild AT, Wood LD, Blackford AL, Donehower RC, Hidalgo M, Schulick RD, Edil BH, Choti MA, Hruban RH, Pawlik TM, Cameron JL, Laheru DA, Iacobuzio-Donahue CA, Wolfgang CL: Correlation of Smad4 status with outcomes in patients receiving erlotinib combined with adjuvant chemoradiation and chemotherapy after resection for pancreatic adenocarcinoma. Int J Radiat Oncol Biol Phys 2013,87(3):458-459. 10.1016/j.ijrobp.2013.06.2039
48. Bashashati A, Ha G, Tone A, Ding J, Prentice LM, Roth A, Rosner J, Shumansky K, Kalloger S, Senz J, Yang W, McConechy M, Melnyk N, Anglesio M, Luk MT, Tse K, Zeng T, Moore R, Zhao Y, Marra MA, Gilks B, Yip S, Huntsman DG, McAlpine JN, Shah SP: Distinct evolutionary trajectories of primary high-grade serous ovarian cancers revealed through spatial mutational profiling. J Pathol 2013,231(1):21-34. 10.1002/path.4230
49. Weinstein IB: Cancer. Addiction to oncogenes-the Achilles heal of cancer. Science 2002,297(5578):63-64. 10.1126/science.1073096
50. Torti D, Trusolino L: Oncogene addiction as a foundational rationale for targeted anti-cancer therapy: promises and perils. EMBO Mol Med 2011,3(11):623-636. 10.1002/emmm.201100176
51. Dhillon KK, Swisher EM, Taniguchi T: Secondary mutations of BRCA1/2 and drug resistance. Cancer Sci 2011,102(4):663-669. 10.1111/j.1349-7006.2010.01840.x
52. Tsang YT, Deavers MT, Sun CC, Kwan SY, Kuo E, Malpica A, Mok SS, Gershenson DM, Wong KK: KRAS (but not BRAF) mutations in ovarian serous borderline tumor are associated with recurrent low-grade serous carcinoma. J Pathol. 2013,231(4):449-456. 10.1002/path.4252
53. Ardighieri L, Zeppernick F, Hannibal CG, Vang R, Cope L, Junge J, Kjaer SK, Kurman RJ, Shih I-M: Mutational analysis of BRAF and KRAS in ovarian serous borderline (atypical proliferative) tumours and associated peritoneal implants. J Pathol 2014, 232:16-22. 10.1002/path.4293
54. Heublein S, Grasse K, Hessel H, Burges A, Lenhard M, Engel J, Kirchner T, Jeschke U, Mayr D: KRAS, BRAF genotyping reveals genetic heterogeneity of ovarian borderline tumors and associated implants. BMC Cancer. 2013, 13:483. 10.1186/1471-2407-13-483
55. Bossard C, Kury S, Jamet P, Senellart H, Airaud F, Ramee JF, Bezieau S, Matysiak-Budnik T, Laboisse CL, Mosnier JF: Delineation of the infrequent mosaicism of KRAS mutational status in metastatic colorectal adenocarcinomas. J Clin Pathol 2012,65(5):466-469. 10.1136/jclinpath-2011-200608
56. Otsuka K, Satoyoshi R, Nanjo H, Miyazawa H, Abe Y, Tanaka M, Yamamoto Y, Shibata H: Acquired/intratumoral mutation of KRAS during metastatic progression of colorectal carcinogenesis. Oncol Lett 2012,3(3):649-653.
57. Singer G, Kurman RJ, Chang HW, Cho SK, Shih IM: Diverse tumorigenic pathways in ovarian serous carcinoma. Am J Pathol 2002,160(4):1223-1228. 10.1016/S0002-9440(10)62549-7
58. Kuo KT, Guan B, Feng Y, Mao TL, Chen X, Jinawath N, Wang Y, Kurman RJ, Shih Ie M, Wang TL: Analysis of DNA copy number alterations in ovarian serous tumors identifies new molecular genetic changes in low-grade and high-grade carcinomas. Cancer Res 2009,69(9):4036-4042. 10.1158/0008-5472.CAN-08-3913
59. Zeller C, Dai W, Curry E, Siddiq A, Walley A, Masrour N, Kitsou-Mylona I, Anderson G, Ghaem-Maghami S, Brown R, El-Bahrawy M: The DNA methylomes of serous borderline tumors reveal subgroups with malignant- or benign-like profiles. Am J Pathol 2013,182(3):668-677. 10.1016/j.ajpath.2012.11.040
60. Keita M, Wang ZQ, Pelletier JF, Bachvarova M, Plante M, Gregoire J, Renaud MC, Mes-Masson AM, Paquet ER, Bachvarov D: Global methylation profiling in serous ovarian cancer is indicative for distinct aberrant DNA methylation signatures associated with tumor aggressiveness and disease progression. Gynecol Oncol 2013,128(2):356-363. 10.1016/j.ygyno.2012.11.036
61. Shih Ie M, Chen L, Wang CC, Gu J, Davidson B, Cope L, Kurman RJ, Xuan J, Wang TL: Distinct DNA methylation profiles in ovarian serous neoplasms and their implications in ovarian carcinogenesis. Am J Obstet Gynecol 2010,203(6):584. e1-22
62. Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, Gronroos E, Martinez P, Matthews N, Stewart A, Tarpey P, Varela I, Phillimore B, Begum S, McDonald NQ, Butler A, Jones D, Raine K, Latimer C, Santos CR, Nohadani M, Eklund AC, Spencer-Dene B, Clark G, Pickering L, Stamp G, Gore M, Szallasi Z, Downward J, Futreal PA, Swanton C: Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 2012,366(10):883-892. 10.1056/NEJMoa1113205
63. Shah SP, Morin RD, Khattra J, Prentice L, Pugh T, Burleigh A, Delaney A, Gelmon K, Guliany R, Senz J, Steidl C, Holt RA, Jones S, Sun M, Leung G, Moore R, Severson T, Taylor GA, Teschendorff AE, Tse K, Turashvili G, Varhol R, Warren RL, Watson P, Zhao Y, Caldas C, Huntsman D, Hirst M, Marra MA, Aparicio S: Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution. Nature 2009,461(7265):809-813. 10.1038/nature08489
64. Ding L, Ley TJ, Larson DE, Miller CA, Koboldt DC, Welch JS, Ritchey JK, Young MA, Lamprecht T, McLellan MD, McMichael JF, Wallis JW, Lu C, Shen D, Harris CC, Dooling DJ, Fulton RS, Fulton LL, Chen K, Schmidt H, Kalicki-Veizer J, Magrini VJ, Cook L, McGrath SD, Vickery TL, Wendl MC, Heath S, Watson MA, Link DC, Tomasson MH, et al.: Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing. Nature 2012,481(7382):506-510. 10.1038/nature10738