Genomic profiling of mitochondrion-rich breast carcinoma: Chromosomal changes may be relevant for mitochondria accumulation and tumour biology

Felipe C. Geyer, Dario De Biase, Maryou B K Lambros, Moira Ragazzi, Maria A. Lopez-Garcia, Rachael Natrajan, Alan Mackay, Ivana Kurelac, Giuseppe Gasparre, Alan Ashworth, Vincenzo Eusebi, Jorge S. Reis-Filho, Giovanni Tallini

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Oncocytic carcinomas are composed of mitochondrion-rich cells. Though recognised by the WHO classification as a histological special type of breast cancer, their status as a discrete pathological entity remains a matter of contention. Given that oncocytic tumours of other anatomical sites display distinct clinico-pathological and molecular features, we sought to define the molecular genetic features of mitochondrion-rich breast tumours and to compare them with a series of histological grade- and oestrogen receptor status-matched invasive ductal carcinomas of no special type. Seventeen mitochondrion-rich breast carcinomas, including nine bona fide oncocytic carcinomas, were profiled with antibodies against oestrogen, progesterone and androgen receptors, HER2, Ki67, GCDFP-15, chromogranin, epithelial membrane antigen, cytokeratin 7, cytokeratin 14, CD68 and mitochondria antigen. These tumours were microdissected and DNA extracted from samples with >70% of tumour cells. Fourteen cases yielded DNA of sufficient quality/quantity and were subjected to high-resolution microarray comparative genomic hybridisation analysis. The genomic profiles were compared to those of 28 grade- and oestrogen receptor status-matched invasive ductal carcinomas of no special type. Oncocytic and other mitochondrion-rich tumours did not differ significantly between themselves. As a group, mitochondrion-rich carcinomas were immunophenotypically heterogenous. Recurrent copy number changes were similar to those described in unselected breast cancers. However, unsupervised and supervised analysis identified a subset of mitochondrion-rich cancers, which often displayed gains of 11q13.1-q13.2 and 19p13. Changes in the latter two chromosomal regions have been shown to be associated with oncocytic tumours of the kidney and thyroid, respectively, and host several nuclear genes with specific mitochondrial function. Our results indicate that in a way akin to oncocytic tumours of other anatomical sites, at least a subset of mitochondrion-rich breast carcinomas may be underpinned by a distinct pattern of chromosomal changes potentially relevant for mitochondria accumulation and constitute a discrete molecular entity.

Original languageEnglish
Pages (from-to)15-28
Number of pages14
JournalBreast Cancer Research and Treatment
Volume132
Issue number1
DOIs
Publication statusPublished - Feb 2012

Fingerprint

Mitochondria
Breast Neoplasms
Neoplasms
Estrogen Receptors
Ductal Carcinoma
Carcinoma
Keratin-14
Keratin-7
Chromogranins
Mucin-1
Comparative Genomic Hybridization
DNA
Androgen Receptors
Progesterone Receptors
Molecular Biology
Thyroid Gland
Kidney
Antibodies
Genes

Keywords

  • aCGH
  • Breast cancer
  • Chromosomal DNA
  • Microarray
  • Mitochondria
  • Oncocytic tumours

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Genomic profiling of mitochondrion-rich breast carcinoma : Chromosomal changes may be relevant for mitochondria accumulation and tumour biology. / Geyer, Felipe C.; De Biase, Dario; Lambros, Maryou B K; Ragazzi, Moira; Lopez-Garcia, Maria A.; Natrajan, Rachael; Mackay, Alan; Kurelac, Ivana; Gasparre, Giuseppe; Ashworth, Alan; Eusebi, Vincenzo; Reis-Filho, Jorge S.; Tallini, Giovanni.

In: Breast Cancer Research and Treatment, Vol. 132, No. 1, 02.2012, p. 15-28.

Research output: Contribution to journalArticle

Geyer, FC, De Biase, D, Lambros, MBK, Ragazzi, M, Lopez-Garcia, MA, Natrajan, R, Mackay, A, Kurelac, I, Gasparre, G, Ashworth, A, Eusebi, V, Reis-Filho, JS & Tallini, G 2012, 'Genomic profiling of mitochondrion-rich breast carcinoma: Chromosomal changes may be relevant for mitochondria accumulation and tumour biology', Breast Cancer Research and Treatment, vol. 132, no. 1, pp. 15-28. https://doi.org/10.1007/s10549-011-1504-4
Geyer, Felipe C. ; De Biase, Dario ; Lambros, Maryou B K ; Ragazzi, Moira ; Lopez-Garcia, Maria A. ; Natrajan, Rachael ; Mackay, Alan ; Kurelac, Ivana ; Gasparre, Giuseppe ; Ashworth, Alan ; Eusebi, Vincenzo ; Reis-Filho, Jorge S. ; Tallini, Giovanni. / Genomic profiling of mitochondrion-rich breast carcinoma : Chromosomal changes may be relevant for mitochondria accumulation and tumour biology. In: Breast Cancer Research and Treatment. 2012 ; Vol. 132, No. 1. pp. 15-28.
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