Allelic Imbalance of 12q22-23 Associated with APAF-1 Locus Correlates with Poor Disease Outcome in Cutaneous Melanoma

Akihide Fujimoto, Hiroya Takeuchi, Bret Taback, Eddy C. Hsueh, David Elashoff, Donald L. Morton, Dave S.B. Hoon

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Abstract

Cutaneous melanoma is a highly aggressive tumor that is relatively resistant to chemotherapy and radiotherapy. This resistance may be in part due to inhibition of apoptosis. Apoptotic protease activating factor-1 (APAF-1), a candidate tumor suppressor gene, mediates p53-induced apoptosis, and its loss promotes oncogenic transformation. To determine whether loss of the APAF-1 locus influences tumor progression, we assessed loss of heterozygosity microsatellites on the APAF-1 locus (12q22-23) in 62 primary and 112 metastatic melanomas. We discovered that frequency of allelic imbalance was significantly higher in metastatic tumors (n = 36 of 98; 37%) than in primary melanomas (n = 10 of 54; 19%; P = 0.02). In metastatic melanomas, APAF-1 loss significantly correlated with a worse prognosis (P < 0.05) in the patients, and its loss during melanoma tumor progression suggests that APAF-1 is a tumor suppressor gene. Furthermore, loss of heterozygosity was frequent in the 12q22-23 chromosome region centromeric to the APAF-1 locus suggesting that other tumor-related genes may be present in the 12q22-23 region. In summary, the study demonstrates that allelic imbalance in the 12q22-23 region is a genomic surrogate of poor disease outcome for cutaneous melanoma patients.

Original languageEnglish
Pages (from-to)2245-2250
Number of pages6
JournalCancer Research
Volume64
Issue number6
DOIs
Publication statusPublished - 2004 Mar 15

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Fujimoto, A., Takeuchi, H., Taback, B., Hsueh, E. C., Elashoff, D., Morton, D. L., & Hoon, D. S. B. (2004). Allelic Imbalance of 12q22-23 Associated with APAF-1 Locus Correlates with Poor Disease Outcome in Cutaneous Melanoma. Cancer Research, 64(6), 2245-2250. https://doi.org/10.1158/0008-5472.CAN-03-2932