665 Associations of BIRC2/3/5 copy number gains with clinicopathological features of acral melanomas in Taiwan

Abstract

Anti-apoptotic molecules can protect melanoma cells from apoptosis, thus enhancing their aggression. One of the factors responsible for the difficulties in engaging the apoptotic cascade efficiently in melanoma is the up-regulation of conserved inhibitor of apoptosis proteins (IAPs). All IAPs share up to three conserved zinc-binding baculoviral IAP repeats domains. The best described members are cIAP1, cIAP2, X-linked IAP, and surviving, which are encoded by Baculovirus inhibitor of apoptosis repeat containing genes (BIRC2, BIRC3, BIRC4, and BIRC5). These proteins are associated with chemoresistance and poor outcome in many cancer types. Acral melanoma is the most common subtype of melanoma in Asians. Our previous report found that frequencies of NRAS/KRAS mutations, altered cell cycle regulation, BIRC2/3/5 copy number gain, and amplification of receptor tyrosine kinase genes were significantly enriched in acral melanomas. In addition, BIRC2/3 copy number gain was only detected in the acral melanomas, and acral melanomas had significantly more BIRC2/3/5 copy number gain than the cutaneous melanomas. Most of BIRC2/3/5 copy number gains were detected in acral melanomas developed in stress-bearing areas. Moreover, the melanomas with BIRC2/3/5 gain were associated with ulceration and greater Breslow thickness. Our further analysis found that cell cycle alteration, BIRC2/3/5 copy number gain, and lymph node status were significant prognostic factors in 45 acral melanoma in a univariate analysis. In a multivariate analysis, altered cell cycle and lymph node status remained the most crucial independent prognostic factors in acral melanomas. We identified BIRC2/3/5 might be a critical determinant of survival in the acral melanoma patients.