Copy number profiling by array comparative genomic hybridization identifies frequently occurring BRCA2-like male breast cancer.
Genomic aberrations can be used to subtype breast cancer. In this study, we investigated DNA copy number (CN) profiles of 69 cases of male breast cancer (MBC) by array comparative genomic hybridization (aCGH) to detect recurrent gains and losses in comparison with female breast cancers (FBC). Further, we classified these profiles as BRCA1-like, BRCA2-like or non-BRCA-like profiles using previous classifiers derived from FBC, and correlated these profiles with pathological characteristics. We observed large CN gains on chromosome arms 1q, 5p, 8q, 10p, 16p, 17q, and chromosomes 20 and X. Large losses were seen on chromosomes/chromosome arms 1p, 6p, 8p, 9, 11q, 13, 14q, 16q, 17p, and 22. The pattern of gains and losses in estrogen receptor positive (ER+) MBC was largely similar to ER+ FBC, except for gains on chromosome X in MBC, which were uncommon in FBC. Out of 69 MBC patients, 15 patients (22%) had a BRCA2-like profile, of which 2 (3%) were also BRCA1-like. One patient (1%) was only BRCA1-like; the remaining 53 (77%) patients were classified as non-BRCA-like. BRCA2-like cases were more often p53 accumulated than non-BRCA-like cases (P = 0.014). In conclusion, the pattern of gains and losses in ER+ MBC was largely similar to that of its ER+ FBC counterpart, except for gains on chromosome X in MBC, which are uncommon in FBC. A significant proportion of MBC has a BRCA2-like aCGH profile, pointing to a potentially hereditary nature, and indicating that they could benefit from a drug regimen targeting BRCA defects as in FBC.
Department of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Hedde D
HD
Biesma
Department of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Philip C
PC
Schouten
Department of Pathology, University Medical Center Utrecht, The Netherlands.
Miangela M
MM
Lacle
Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Joyce
J
Sanders
Genomics Core Facility, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Wim
W
Brugman
Genomics Core Facility, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Ron
R
Kerkhoven
Data Center, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Ingrid
I
Mandjes
Department of Pathology, University Medical Center Utrecht, The Netherlands.
Petra
P
van der Groep
Department of Pathology, University Medical Center Utrecht, The Netherlands.
Paul J
PJ
van Diest
Department of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands.|Department of Pathology, University Medical Center Utrecht, The Netherlands.|Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Sabine C
SC
Linn
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics*; D018567:Breast Neoplasms, Male / Q000145:classification* / Q000235:genetics* / Q000473:pathology; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization / Q000379:methods; D056915:DNA Copy Number Variations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D019313:BRCA1 Protein; D024682:BRCA2 Protein; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53