Adenoid cystic carcinomas constitute a genomically distinct subgroup of triple-negative and basal-like breast cancers

Daniel Wetterskog, Maria Angeles Lopez-Garcia, Maryou B Lambros, Roger A'Hern, Felipe C Geyer, Fernanda Milanezi, Maria C Cabral, Rachael Natrajan, Arnaud Gauthier, Kai-Keen Shiu, Nicholas Orr, Sami Shousha, Zoran Gatalica, Alan Mackay, Jose Palacios, Jorge S Reis-Filho, Britta Weigelt

Research output: Contribution to journalArticlepeer-review

101 Citations (Scopus)

Abstract

Adenoid cystic carcinoma (AdCC) is a rare form of triple-negative and basal-like breast cancer that has an indolent clinical behaviour. Four breast AdCCs were recently shown to harbour the recurrent chromosomal translocation t(6;9)(q22-23;p23-24), which leads to the formation of the MYB-NFIB fusion gene. Our aims were (i) to determine the prevalence of the MYB-NFIB fusion gene in AdCCs of the breast; (ii) to characterize the gene copy number aberrations found in AdCCs; and (iii) to determine whether AdCCs are genomically distinct from histological grade-matched or triple-negative and basal-like invasive ductal carcinomas of no special type (IDC-NSTs). The presence of the MYB-NFIB fusion gene was investigated in 13 AdCCs of the breast by fluorescence in situ hybridization (FISH) and reverse transcriptase-PCR (RT-PCR), and MYB and BRCA1 RNA expression was determined by quantitative RT-PCR. Fourteen AdCCs, 14 histological grade-matched IDC-NSTs, and 14 IDC-NSTs of triple-negative and basal-like phenotype were microdissected and subjected to high-resolution microarray-based comparative genomic hybridization (aCGH). The MYB-NFIB fusion gene was detected in all but one AdCC. aCGH analysis demonstrated a relatively low number of copy number aberrations and a lack of recurrent amplifications in breast AdCCs. Contrary to grade-matched IDC-NSTs, AdCCs lacked 1q gains and 16q losses, and in contrast with basal-like IDC-NSTs, AdCCs displayed fewer gene copy number aberrations and expressed MYB and BRCA1 at significantly higher levels. Breast AdCCs constitute an entity distinct from grade-matched and triple-negative and basal-like IDC-NSTs, emphasizing the importance of histological subtyping of triple-negative and basal-like breast carcinomas.

Original languageEnglish
Pages (from-to)84-96
Number of pages13
JournalJournal of Pathology
Volume226
Issue number1
DOIs
Publication statusPublished - Jan 2012

Keywords

  • Breast Neoplasms
  • Carcinoma, Adenoid Cystic
  • Carcinoma, Ductal, Breast
  • Female
  • Gene Dosage
  • Gene Expression Profiling
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Microdissection
  • Oncogene Proteins, Fusion
  • Receptor, ErbB-3
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tissue Array Analysis
  • Journal Article
  • Research Support, Non-U.S. Gov't

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