Biesma Hedde D, Schouten Philip C, Lacle Miangela M, Sanders Joyce, Brugman Wim, Kerkhoven Ron, Mandjes Ingrid, van der Groep Petra, van Diest Paul J, Linn Sabine C
Department of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Department of Pathology, University Medical Center Utrecht, The Netherlands.
Genes Chromosomes Cancer. 2015 Dec;54(12):734-44. doi: 10.1002/gcc.22284. Epub 2015 Sep 10.
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.
基因组畸变可用于对乳腺癌进行亚型分类。在本研究中，我们通过阵列比较基因组杂交（aCGH）研究了69例男性乳腺癌（MBC）的DNA拷贝数（CN）谱，以检测与女性乳腺癌（FBC）相比的复发性增益和缺失。此外，我们使用先前从FBC得出的分类器将这些谱分类为BRCA1样、BRCA2样或非BRCA样谱，并将这些谱与病理特征相关联。我们观察到染色体臂1q、5p、8q、10p、16p、17q以及染色体20和X上有大量CN增益。在染色体/染色体臂1p、6p、8p、9、11q、13、14q、16q、17p和22上观察到大量缺失。雌激素受体阳性（ER+）MBC的增益和缺失模式与ER+ FBC基本相似，除了MBC中X染色体上的增益在FBC中不常见。在69例MBC患者中，15例（22%）具有BRCA2样谱，其中2例（3%）也为BRCA1样。1例患者（1%）仅为BRCA1样；其余53例（77%）患者被分类为非BRCA样。BRCA2样病例比非BRCA样病例更常出现p53积累（P = 0.014）。总之，ER+ MBC的增益和缺失模式与其ER+ FBC对应物基本相似，除了MBC中X染色体上的增益在FBC中不常见。相当一部分MBC具有BRCA2样aCGH谱，表明其具有潜在的遗传性，并表明它们可能像FBC一样从针对BRCA缺陷的药物治疗方案中获益。
