Analysis of gene copy number alterations by multiplex ligation-dependent probe amplification in columnar cell lesions of the breast

Anoek H J Verschuur-Maes, Cathy B. Moelans, Peter C. De Bruin, Paul J. Van Diest

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Columnar cell lesions (CCLs) are possible precursors of breast cancer, but little is known about the role of breast cancer-related genes in the progression of CCL to invasive breast cancer. Methods: Gene copy numbers of 17 breast cancer-related genes were analyzed using Multiplex Ligation-dependent Probe Amplification (MLPA) in CCL (N∈=∈28), ductal carcinoma in situ (DCIS) grade I likely originating from CCL (N∈=∈5), and paired CCL (N∈=∈14/28) with DCIS (N∈=∈7) and/or invasive carcinoma (N∈=∈13). The genes included were BIRC5, C11orf30, CCND1, CCNE1, CDH1, CPD, EGFR, ERBB2, ESR1, FGFR1, IKBKB, MAPT, MED1, MTDH, MYC, TOP2A and TRAF4. Results: No high level gene amplifications were observed in CCL, but copy number gains were encountered for the C11orf30 (3/28), MYC, CPD, MTDH (2/28), and CCND1, CCNE1, ESR1 and TOP2A genes (1/28). In addition, CDH1 showed loss in 2/28 and TOP2A in 1/28 cases. CCLs with or without atypia exhibited comparable numbers of copy number changes (p∈=∈0.312). Overall, the frequency of gene copy number changes increased from CCL towards DCIS and invasive carcinoma (p∈=∈0.004). Also in the cases with synchronous lesions, the CCLs exhibited fewer copy number changes than the DCIS/invasive carcinomas. Conclusions: CCLs carry copy number changes of several known breast cancer-related genes, thereby substantiating their role in breast carcinogenesis. Among them, CCND1 and ESR1 copy number gains and CDH1 copy number losses are of particular interest. Since the copy number changes observed were more prevalent in DCIS and invasive carcinoma than in CCL, the corresponding gene alterations may represent rather late occurring events in low nuclear grade breast carcinogenesis.

Original languageEnglish (US)
Pages (from-to)147-154
Number of pages8
JournalCellular Oncology
Volume37
Issue number2
DOIs
StatePublished - 2014
Externally publishedYes

Keywords

  • Breast
  • Columnar cell lesions
  • Flat epithelial atypia
  • MLPA
  • Multiplex ligation-dependent probe amplification
  • Oncogenes

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Oncology
  • Medicine(all)

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