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Copy number profiling of oncogenes in ductal carcinoma in situ of the male breast.
Endocrine-related Cancer 2018 March
Characterizing male breast cancer (BC) and unraveling male breast carcinogenesis is challenging because of the rarity of this disease. We investigated copy number status of 22 BC-related genes in 18 cases of pure ductal carcinoma in situ (DCIS) and in 49 cases of invasive carcinoma (IC) with adjacent DCIS (DCIS-AIC) in males using multiplex ligation-dependent probe amplification (MLPA). Results were compared to female BC and correlated with survival. Overall, copy number ratio and aberration frequency including all 22 genes showed no significant difference between the 3 groups. Individual unpaired analysis revealed a significantly higher MTDH copy number ratio in IC compared to DCIS-AIC and pure DCIS ( P = 0.009 and P = 0.038, respectively). ADAM9 showed a significantly lower copy number aberration frequency in male BC, compared to female BC ( P = 0.020). In DCIS-AIC, MTDH , CPD , CDC6 and TOP2A showed a lower frequency of copy number increase in males compared to females ( P < 0.001 for all 4 genes). In IC, CPD gain and CCNE1 gain were independent predictors of poor overall survival. In conclusion, male DCIS and IC showed a similar copy number profile for 21 out of 22 interrogated BC-related genes, illustrating their clonal relation and the genetically advanced state of male DCIS. MTDH showed a higher copy number ratio in IC compared to adjacent and pure DCIS and may therefore play a role in male breast carcinogenesis. Differences were detected between male and female DCIS for 4 genes pointing to differences in breast carcinogenesis between the sexes.
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