PMID- 25906114 OWN - NLM STAT- MEDLINE DCOM- 20160322 LR - 20181113 IS - 2211-3436 (Electronic) IS - 2211-3428 (Print) IS - 2211-3428 (Linking) VI - 38 IP - 3 DP - 2015 Jun TI - Chromosome 17 copy number changes in male breast cancer. PG - 237-45 LID - 10.1007/s13402-015-0227-7 [doi] AB - BACKGROUND: Overall, HER2-amplified female breast cancer (FBC) is associated with a high grade, an aggressive phenotype and a poor prognosis. In male breast cancer (MBC) amplification of HER2, located on chromosome 17, occurs at a lower frequency than in FBC, where it is part of complex rearrangements. So far, only few studies have addressed the occurrence of chromosome 17 alterations in small MBC cohorts. METHODS: Multiplex ligation-dependent probe amplification (MLPA) and fluorescence in situ hybridization (FISH) were used to detect and characterize copy number changes on chromosome 17 in a cohort of 139 MBC. The results obtained were compared to those in FBC, and were correlated with clinicopathological features and patient outcome data. RESULTS: We observed a lower frequency of chromosome 17 copy number changes with less complex rearrangement patterns in MBC compared to FBC. Chromosome 17 changes in MBC included gains of 17q and losses of 17p. Whole chromosome 17 polyploidies were not encountered. Two recurrent chromosome 17 amplicons were detected: on 17q12 (encompassing the NEUROD2, HER2, GRB7 and IKZF3 gens) and on 17q23.1 (encompassing the MIR21 and RPS6KB1 genes). Whole arm copy number gains of 17q were associated with decreased 5 year survival rates (p = 0.010). Amplification of HER2 was associated with a high tumor grade, but did not predict patient survival. Although copy number gains of HER2 and NEUROD2 were associated with a high tumor grade, a high mitotic count and a decreased 5 year survival rate (p = 0.015), only tumor size and NEUROD2 copy number gains emerged as independent prognostic factors. CONCLUSIONS: In MBC chromosome 17 shows less complex rearrangements and fewer copy number changes compared to FBC. Frequent gains of 17q, encompassing two distinct amplicons, and losses of 17p were observed, but no whole chromosome 17 polyploidies. Only NEUROD2 gains seem to have an independent prognostic impact. These results suggest different roles of chromosome 17 aberrations in male versus female breast carcinogenesis. FAU - Lacle, Miangela M AU - Lacle MM AD - Department of Pathology, University Medical Center Utrecht, PO Box 85500, 3508 GA, Utrecht, The Netherlands. FAU - Moelans, Cathy B AU - Moelans CB FAU - Kornegoor, Robert AU - Kornegoor R FAU - van der Pol, Carmen AU - van der Pol C FAU - Witkamp, Arjen J AU - Witkamp AJ FAU - van der Wall, Elsken AU - van der Wall E FAU - Rueschoff, Josef AU - Rueschoff J FAU - Buerger, Horst AU - Buerger H FAU - van Diest, Paul J AU - van Diest PJ LA - eng PT - Journal Article DEP - 20150424 PL - Netherlands TA - Cell Oncol (Dordr) JT - Cellular oncology (Dordrecht) JID - 101552938 SB - IM MH - Adult MH - Aged MH - Breast Neoplasms/genetics MH - Breast Neoplasms, Male/*genetics MH - Chromosomes, Human, Pair 17/*genetics MH - Female MH - *Gene Dosage MH - Humans MH - Male MH - Middle Aged MH - Multiplex Polymerase Chain Reaction PMC - PMC4445249 EDAT- 2015/04/24 06:00 MHDA- 2016/03/24 06:00 PMCR- 2015/04/24 CRDT- 2015/04/24 06:00 PHST- 2015/04/01 00:00 [accepted] PHST- 2015/04/24 06:00 [entrez] PHST- 2015/04/24 06:00 [pubmed] PHST- 2016/03/24 06:00 [medline] PHST- 2015/04/24 00:00 [pmc-release] AID - 227 [pii] AID - 10.1007/s13402-015-0227-7 [doi] PST - ppublish SO - Cell Oncol (Dordr). 2015 Jun;38(3):237-45. doi: 10.1007/s13402-015-0227-7. Epub 2015 Apr 24.