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01-06-2012 | Preclinical study

Identification of copy number alterations associated with the progression of DCIS to invasive ductal carcinoma

Authors: Clint E. Johnson, Kylie L. Gorringe, Ella R. Thompson, Ken Opeskin, Samantha E. Boyle, Yuker Wang, Prue Hill, G. Bruce Mann, Ian G. Campbell

Published in: Breast Cancer Research and Treatment | Issue 3/2012

Abstract

Ductal carcinoma in situ (DCIS) is a non-obligate precursor to invasive ductal carcinoma (IDC). Annotation of the genetic differences between the two lesions may assist in the identification of genes that promote the invasive phenotype. Synchronous DCIS and IDC cells were microdissected from FFPE tissue and analysed by molecular inversion probe (MIP) copy number arrays. Matched IDC and DCIS showed highly similar copy number profiles (average of 83% of the genome shared) indicating a common clonal origin although there is evidence that the DCIS continues to evolve in parallel with the co-existing IDC. Four chromosomal regions of loss (3q, 6q, 8p and 11q) and four regions of gain (5q, 16p, 19q and 20) were recurrently affected in IDC but not in DCIS. CCND1 and MYC showed increased amplitude of gain in IDC. One region of loss (17p11.2) was specific to DCIS. IDC-specific regions include genes with previous links to breast cancer progression and potential therapeutic targets such as AXL, SPHK1 and PLAUR.

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Leonard GD, Swain SM (2004) Ductal carcinoma in situ, complexities and challenges. J Natl Cancer Inst 96(12):906–920PubMedCrossRef

Reis-Filho JS, Lakhani SR (2003) The diagnosis and management of pre-invasive breast disease: genetic alterations in pre-invasive lesions. Breast Cancer Res 5(6):313–319. doi:10.1186/bcr650 PubMedCrossRef

Kerlikowske K, Molinaro AM, Gauthier ML, Berman HK, Waldman F, Bennington J, Sanchez H, Jimenez C, Stewart K, Chew K, Ljung BM, Tlsty TD (2010) Biomarker expression and risk of subsequent tumors after initial ductal carcinoma in situ diagnosis. J Natl Cancer Inst 102(9):627–637. doi:10.1093/jnci/djq101 PubMedCrossRef

Gauthier ML, Berman HK, Miller C, Kozakeiwicz K, Chew K, Moore D, Rabban J, Chen YY, Kerlikowske K, Tlsty TD (2007) Abrogated response to cellular stress identifies DCIS associated with subsequent tumor events and defines basal-like breast tumors. Cancer Cell 12(5):479–491. doi:10.1016/j.ccr.2007.10.017 PubMedCrossRef

Farabegoli F, Champeme MH, Bieche I, Santini D, Ceccarelli C, Derenzini M, Lidereau R (2002) Genetic pathways in the evolution of breast ductal carcinoma in situ. J Pathol 196(3):280–286PubMedCrossRef

Maitra A, Wistuba II, Washington C, Virmani AK, Ashfaq R, Milchgrub S, Gazdar AF, Minna JD (2001) High-resolution chromosome 3p allelotyping of breast carcinomas and precursor lesions demonstrates frequent loss of heterozygosity and a discontinuous pattern of allele loss. Am J Pathol 159(1):119–130PubMedCrossRef

Zhuang Z, Merino MJ, Chuaqui R, Liotta LA, Emmert-Buck MR (1995) Identical allelic loss on chromosome 11q13 in microdissected in situ and invasive human breast cancer. Cancer Res 55(3):467–471PubMed

Castro NP, Osorio CA, Torres C, Bastos EP, Mourao-Neto M, Soares FA, Brentani HP, Carraro DM (2008) Evidence that molecular changes in cells occur before morphological alterations during the progression of breast ductal carcinoma. Breast Cancer Res 10(5):R87. doi:10.1186/bcr2157 PubMedCrossRef

Dalgin GS, Alexe G, Scanfeld D, Tamayo P, Mesirov JP, Ganesan S, DeLisi C, Bhanot G (2007) Portraits of breast cancer progression. BMC Bioinformatics 8:291. doi:10.1186/1471-2105-8-291 PubMedCrossRef

10.

Ma XJ, Salunga R, Tuggle JT, Gaudet J, Enright E, McQuary P, Payette T, Pistone M, Stecker K, Zhang BM, Zhou YX, Varnholt H, Smith B, Gadd M, Chatfield E, Kessler J, Baer TM, Erlander MG, Sgroi DC (2003) Gene expression profiles of human breast cancer progression. Proc Natl Acad Sci USA 100(10):5974–5979. doi:10.1073/pnas.0931261100 PubMedCrossRef

11.

Waldman FM, DeVries S, Chew KL, Moore DH 2nd, Kerlikowske K, Ljung BM (2000) Chromosomal alterations in ductal carcinomas in situ and their in situ recurrences. J Natl Cancer Inst 92(4):313–320PubMedCrossRef

12.

Gao Y, Niu Y, Wang X, Wei L, Lu S (2009) Genetic changes at specific stages of breast cancer progression detected by comparative genomic hybridization. J Mol Med 87(2):145–152. doi:10.1007/s00109-008-0408-1 PubMedCrossRef

13.

O’Connell P, Pekkel V, Fuqua SA, Osborne CK, Clark GM, Allred DC (1998) Analysis of loss of heterozygosity in 399 premalignant breast lesions at 15 genetic loci. J Natl Cancer Inst 90(9):697–703PubMedCrossRef

14.

Xu S, Wei B, Zhang H, Qing M, Bu H (2008) Evidence of chromosomal alterations in pure usual ductal hyperplasia as a breast carcinoma precursor. Oncol Rep 19(6):1469–1475PubMed

15.

Robanus-Maandag EC, Bosch CA, Kristel PM, Hart AA, Faneyte IF, Nederlof PM, Peterse JL, van de Vijver MJ (2003) Association of C-MYC amplification with progression from the in situ to the invasive stage in C-MYC-amplified breast carcinomas. J Pathol 201(1):75–82. doi:10.1002/path.1385 PubMedCrossRef

16.

Wang Y, Carlton VE, Karlin-Neumann G, Sapolsky R, Zhang L, Moorhead M, Wang ZC, Richardson AL, Warren R, Walther A, Bondy M, Sahin A, Krahe R, Tuna M, Thompson PA, Spellman PT, Gray JW, Mills GB, Faham M (2009) High quality copy number and genotype data from FFPE samples using molecular inversion probe (MIP) microarrays. BMC Med Genomics 2:8. doi:10.1186/1755-8794-2-8 PubMedCrossRef

17.

Wu L, Patten N, Yamashiro CT, Chui B (2002) Extraction and amplification of DNA from formalin-fixed, paraffin-embedded tissues. Appl Immunohistochem Mol Morphol 10(3):269–274PubMedCrossRef

18.

Wang Y, Moorhead M, Karlin-Neumann G, Wang NJ, Ireland J, Lin S, Chen C, Heiser LM, Chin K, Esserman L, Gray JW, Spellman PT, Faham M (2007) Analysis of molecular inversion probe performance for allele copy number determination. Genome Biol 8(11):R246. doi:10.1186/gb-2007-8-11-r246 PubMedCrossRef

19.

Gorringe KL, George J, Anglesio MS, Ramakrishna M, Etemadmoghadam D, Cowin P, Sridhar A, Williams LH, Boyle SE, Yanaihara N, Okamoto A, Urashima M, Smyth GK, Campbell IG, Bowtell DD (2010) Copy number analysis identifies novel interactions between genomic loci in ovarian cancer. PLoS One 5(9). doi:10.1371/journal.pone.0011408

20.

Marioni JC, Thorne NP, Valsesia A, Fitzgerald T, Redon R, Fiegler H, Andrews TD, Stranger BE, Lynch AG, Dermitzakis ET, Carter NP, Tavare S, Hurles ME (2007) Breaking the waves: improved detection of copy number variation from microarray-based comparative genomic hybridization. Genome Biol 8(10):R228. doi:10.1186/gb-2007-8-10-r228 PubMedCrossRef

21.

Chin K, DeVries S, Fridlyand J, Spellman PT, Roydasgupta R, Kuo WL, Lapuk A, Neve RM, Qian Z, Ryder T, Chen F, Feiler H, Tokuyasu T, Kingsley C, Dairkee S, Meng Z, Chew K, Pinkel D, Jain A, Ljung BM, Esserman L, Albertson DG, Waldman FM, Gray JW (2006) Genomic and transcriptional aberrations linked to breast cancer pathophysiologies. Cancer Cell 10(6):529–541. doi:10.1016/j.ccr.2006.10.009 PubMedCrossRef

22.

Chin SF, Teschendorff AE, Marioni JC, Wang Y, Barbosa-Morais NL, Thorne NP, Costa JL, Pinder SE, van de Wiel MA, Green AR, Ellis IO, Porter PL, Tavare S, Brenton JD, Ylstra B, Caldas C (2007) High-resolution aCGH and expression profiling identifies a novel genomic subtype of ER negative breast cancer. Genome Biol 8(10):R215. doi:10.1186/gb-2007-8-10-r215 PubMedCrossRef

23.

Haverty PM, Fridlyand J, Li L, Getz G, Beroukhim R, Lohr S, Wu TD, Cavet G, Zhang Z, Chant J (2008) High-resolution genomic and expression analyses of copy number alterations in breast tumors. Genes Chromosomes Cancer 47(6):530–542. doi:10.1002/gcc.20558 PubMedCrossRef

24.

Jonsson G, Staaf J, Vallon-Christersson J, Ringner M, Holm K, Hegardt C, Gunnarsson H, Fagerholm R, Strand C, Agnarsson BA, Kilpivaara O, Luts L, Heikkila P, Aittomaki K, Blomqvist C, Loman N, Malmstrom P, Olsson H, Johannsson OT, Arason A, Nevanlinna H, Barkardottir RB, Borg A (2010) Genomic subtypes of breast cancer identified by array-comparative genomic hybridization display distinct molecular and clinical characteristics. Breast Cancer Res 12(3):R42. doi:10.1186/bcr2596 PubMedCrossRef

25.

Natrajan R, Lambros MB, Rodriguez-Pinilla SM, Moreno-Bueno G, Tan DS, Marchio C, Vatcheva R, Rayter S, Mahler-Araujo B, Fulford LG, Hungermann D, Mackay A, Grigoriadis A, Fenwick K, Tamber N, Hardisson D, Tutt A, Palacios J, Lord CJ, Buerger H, Ashworth A, Reis-Filho JS (2009) Tiling path genomic profiling of grade 3 invasive ductal breast cancers. Clin Cancer Res 15(8):2711–2722. doi:10.1158/1078-0432.CCR-08-1878 PubMedCrossRef

26.

Turner N, Lambros MB, Horlings HM, Pearson A, Sharpe R, Natrajan R, Geyer FC, van Kouwenhove M, Kreike B, Mackay A, Ashworth A, van de Vijver MJ, Reis-Filho JS (2010) Integrative molecular profiling of triple negative breast cancers identifies amplicon drivers and potential therapeutic targets. Oncogene 29(14):2013–2023. doi:10.1038/onc.2009.489 PubMedCrossRef

27.

Kadota M, Sato M, Duncan B, Ooshima A, Yang HH, Diaz-Meyer N, Gere S, Kageyama S, Fukuoka J, Nagata T, Tsukada K, Dunn BK, Wakefield LM, Lee MP (2009) Identification of novel gene amplifications in breast cancer and coexistence of gene amplification with an activating mutation of PIK3CA. Cancer Res 69(18):7357–7365. doi:10.1158/0008-5472.CAN-09-0064 PubMedCrossRef

28.

Thompson PA, Brewster AM, Kim-Anh D, Baladandayuthapani V, Broom BM, Edgerton ME, Hahn KM, Murray JL, Sahin A, Tsavachidis S, Wang Y, Zhang L, Hortobagyi GN, Mills GB, Bondy ML (2011) Selective genomic copy number imbalances and probability of recurrence in early-stage breast cancer. PLoS One 6(8):e23543PubMedCrossRef

29.

Muggerud AA, Hallett M, Johnsen H, Kleivi K, Zhou W, Tahmasebpoor S, Amini RM, Botling J, Borresen-Dale AL, Sorlie T, Warnberg F (2010) Molecular diversity in ductal carcinoma in situ (DCIS) and early invasive breast cancer. Mol Oncol 4(4):357–368. doi:10.1016/j.molonc.2010.06.007 PubMedCrossRef

30.

Schuetz CS, Bonin M, Clare SE, Nieselt K, Sotlar K, Walter M, Fehm T, Solomayer E, Riess O, Wallwiener D, Kurek R, Neubauer HJ (2006) Progression-specific genes identified by expression profiling of matched ductal carcinomas in situ and invasive breast tumors, combining laser capture microdissection and oligonucleotide microarray analysis. Cancer Res 66(10):5278–5286. doi:10.1158/0008-5472.CAN-05-4610 PubMedCrossRef

31.

Balleine RL, Webster LR, Davis S, Salisbury EL, Palazzo JP, Schwartz GF, Cornfield DB, Walker RL, Byth K, Clarke CL, Meltzer PS (2008) Molecular grading of ductal carcinoma in situ of the breast. Clin Cancer Res 14(24):8244–8252. doi:10.1158/1078-0432.CCR-08-0939 PubMedCrossRef

32.

Vincent-Salomon A, Lucchesi C, Gruel N, Raynal V, Pierron G, Goudefroye R, Reyal F, Radvanyi F, Salmon R, Thiery JP, Sastre-Garau X, Sigal-Zafrani B, Fourquet A, Delattre O (2008) Integrated genomic and transcriptomic analysis of ductal carcinoma in situ of the breast. Clin Cancer Res 14(7):1956–1965. doi:10.1158/1078-0432.CCR-07-1465 PubMedCrossRef

33.

Yao J, Weremowicz S, Feng B, Gentleman RC, Marks JR, Gelman R, Brennan C, Polyak K (2006) Combined cDNA array comparative genomic hybridization and serial analysis of gene expression analysis of breast tumor progression. Cancer Res 66(8):4065–4078. doi:10.1158/0008-5472.CAN-05-4083 PubMedCrossRef

34.

Burkhardt L, Grob TJ, Hermann I, Burandt E, Choschzick M, Janicke F, Muller V, Bokemeyer C, Simon R, Sauter G, Wilczak W, Lebeau A (2010) Gene amplification in ductal carcinoma in situ of the breast. Breast Cancer Res Treat 123(3):757–765. doi:10.1007/s10549-009-0675-8 PubMedCrossRef

35.

Tyndall JD, Kelso MJ, Clingan P, Ranson M (2008) Peptides and small molecules targeting the plasminogen activation system: towards prophylactic anti-metastasis drugs for breast cancer. Recent Pat Anticancer Drug Discov 3(1):1–13PubMedCrossRef

36.

Antoon JW, Meacham WD, Bratton MR, Slaughter EM, Rhodes LV, Ashe HB, Wiese TE, Burow ME, Beckman BS (2011) Pharmacological inhibition of sphingosine kinase isoforms alters estrogen receptor signaling in human breast cancer. J Mol Endocrinol 46(3):205–216. doi:10.1530/JME-10-0116 PubMedCrossRef

37.

Ruckhaberle E, Rody A, Engels K, Gaetje R, von Minckwitz G, Schiffmann S, Grosch S, Geisslinger G, Holtrich U, Karn T, Kaufmann M (2008) Microarray analysis of altered sphingolipid metabolism reveals prognostic significance of sphingosine kinase 1 in breast cancer. Breast Cancer Res Treat 112(1):41–52. doi:10.1007/s10549-007-9836-9 PubMedCrossRef

38.

Gjerdrum C, Tiron C, Hoiby T, Stefansson I, Haugen H, Sandal T, Collett K, Li S, McCormack E, Gjertsen BT, Micklem DR, Akslen LA, Glackin C, Lorens JB (2010) Axl is an essential epithelial-to-mesenchymal transition-induced regulator of breast cancer metastasis and patient survival. Proc Natl Acad Sci USA 107(3):1124–1129. doi:10.1073/pnas.0909333107 PubMedCrossRef

39.

Beroukhim R, Mermel CH, Porter D, Wei G, Raychaudhuri S, Donovan J, Barretina J, Boehm JS, Dobson J, Urashima M, Mc Henry KT, Pinchback RM, Ligon AH, Cho YJ, Haery L, Greulich H, Reich M, Winckler W, Lawrence MS, Weir BA, Tanaka KE, Chiang DY, Bass AJ, Loo A, Hoffman C, Prensner J, Liefeld T, Gao Q, Yecies D, Signoretti S, Maher E, Kaye FJ, Sasaki H, Tepper JE, Fletcher JA, Tabernero J, Baselga J, Tsao MS, Demichelis F, Rubin MA, Janne PA, Daly MJ, Nucera C, Levine RL, Ebert BL, Gabriel S, Rustgi AK, Antonescu CR, Ladanyi M, Letai A, Garraway LA, Loda M, Beer DG, True LD, Okamoto A, Pomeroy SL, Singer S, Golub TR, Lander ES, Getz G, Sellers WR, Meyerson M (2010) The landscape of somatic copy-number alteration across human cancers. Nature 463(7283):899–905. doi:10.1038/nature08822 PubMedCrossRef

40.

Forbes SA, Bindal N, Bamford S, Cole C, Kok CY, Beare D, Jia M, Shepherd R, Leung K, Menzies A, Teague JW, Campbell PJ, Stratton MR, Futreal PA (2011) COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer. Nucleic Acids Res 39(Database issue):D945–D950. doi:10.1093/nar/gkq929 PubMedCrossRef

41.

Farrell C, Crimm H, Meeh P, Croshaw R, Barbar T, Vandersteenhoven JJ, Butler W, Buckhaults P (2008) Somatic mutations to CSMD1 in colorectal adenocarcinomas. Cancer Biol Ther 7(4):609–613PubMedCrossRef

42.

Furuta E, Pai SK, Zhan R, Bandyopadhyay S, Watabe M, Mo YY, Hirota S, Hosobe S, Tsukada T, Miura K, Kamada S, Saito K, Iiizumi M, Liu W, Ericsson J, Watabe K (2008) Fatty acid synthase gene is up-regulated by hypoxia via activation of Akt and sterol regulatory element binding protein-1. Cancer Res 68(4):1003–1011. doi:10.1158/0008-5472.CAN-07-2489 PubMedCrossRef

43.

Dupont Jensen J, Laenkholm AV, Knoop A, Ewertz M, Bandaru R, Liu W, Hackl W, Barrett JC, Gardner H (2011) PIK3CA mutations may be discordant between primary and corresponding metastatic disease in breast cancer. Clin Cancer Res 17(4):667–677. doi:10.1158/1078-0432.CCR-10-1133 PubMedCrossRef

44.

Lopez-Garcia MA, Geyer FC, Lacroix-Triki M, Marchio C, Reis-Filho JS (2010) Breast cancer precursors revisited: molecular features and progression pathways. Histopathology 57(2):171–192. doi:10.1111/j.1365-2559.2010.03568.x PubMedCrossRef

45.

Espina V, Mariani BD, Gallagher RI, Tran K, Banks S, Wiedemann J, Huryk H, Mueller C, Adamo L, Deng J, Petricoin EF, Pastore L, Zaman S, Menezes G, Mize J, Johal J, Edmiston K, Liotta LA (2010) Malignant precursor cells pre-exist in human breast DCIS and require autophagy for survival. PLoS One 5(4):e10240. doi:10.1371/journal.pone.0010240 PubMedCrossRef

Title: Identification of copy number alterations associated with the progression of DCIS to invasive ductal carcinoma
Authors: Clint E. Johnson
Kylie L. Gorringe
Ella R. Thompson
Ken Opeskin
Samantha E. Boyle
Yuker Wang
Prue Hill
G. Bruce Mann
Ian G. Campbell
Publication date: 01-06-2012
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 3/2012
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-011-1835-1

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