TY - JOUR
T1 - Array-CGH reveals recurrent genomic changes in merkel cell carcinoma including amplification of L-Myc
AU - Paulson, Kelly G.
AU - Lemos, Bianca D.
AU - Feng, Bin
AU - Jaimes, Natalia
AU - Pẽas, Pablo F.
AU - Bi, Xiaohui
AU - Maher, Elizabeth
AU - Cohen, Lisa
AU - Leonard, J. Helen
AU - Granter, Scott R.
AU - Chin, Lynda
AU - Nghiem, Paul
N1 - Funding Information:
We thank the Bomsztyk Lab at the University of Washington for advice and reagents and the Eisenman Lab at the Fred Hutchison Cancer Research Center for the gift of an L-Myc plasmid. Array-CGH profiling was performed at the Belfer Center for Cancer Genomics in the Center for Applied Cancer Science at Dana-Farber Cancer Institute. This project was supported by the Harvard Skin Cancer SPORE, NIH-K02-AR050993, the American Cancer Society Jerry Wachter Fund for MCC Research, the Skin Cancer Foundation, and the MCC Patient Gift Fund at the University of Washington.
PY - 2009/6
Y1 - 2009/6
N2 - Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer with poorly characterized genetics. We performed high resolution comparative genomic hybridization on 25 MCC specimens using a high-density oligonucleotide microarray. Tumors frequently carried extra copies of chromosomes 1, 3q, 5p, and 6 and lost chromosomes 3p, 4, 5q, 7, 10, and 13. MCC tumors with less genomic aberration were associated with improved survival (P0.04). Tumors from 13 of 22 MCC patients had detectable Merkel cell polyomavirus DNA, and these tumors had fewer genomic deletions. Three regions of genomic alteration were of particular interest: a deletion of 5q12-21 occurred in 26 of tumors, a deletion of 13q14-21 was recurrent in 26 of tumors and contains the well-characterized tumor suppressor RB1, and a previously unreported focal amplification at 1p34 was present in 39 of tumors and centers on L-Myc (MYCL1). L-Myc is related to the c-Myc proto-oncogene, has transforming activity, and is amplified in the closely related small cell lung cancer. Normal skin showed no L-Myc expression, whereas 44 MCC specimens tested expressed L-Myc RNA in relative proportion to the DNA copy number gain. These findings suggest several genes that may contribute to MCC pathogenesis, most notably L-Myc.
AB - Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer with poorly characterized genetics. We performed high resolution comparative genomic hybridization on 25 MCC specimens using a high-density oligonucleotide microarray. Tumors frequently carried extra copies of chromosomes 1, 3q, 5p, and 6 and lost chromosomes 3p, 4, 5q, 7, 10, and 13. MCC tumors with less genomic aberration were associated with improved survival (P0.04). Tumors from 13 of 22 MCC patients had detectable Merkel cell polyomavirus DNA, and these tumors had fewer genomic deletions. Three regions of genomic alteration were of particular interest: a deletion of 5q12-21 occurred in 26 of tumors, a deletion of 13q14-21 was recurrent in 26 of tumors and contains the well-characterized tumor suppressor RB1, and a previously unreported focal amplification at 1p34 was present in 39 of tumors and centers on L-Myc (MYCL1). L-Myc is related to the c-Myc proto-oncogene, has transforming activity, and is amplified in the closely related small cell lung cancer. Normal skin showed no L-Myc expression, whereas 44 MCC specimens tested expressed L-Myc RNA in relative proportion to the DNA copy number gain. These findings suggest several genes that may contribute to MCC pathogenesis, most notably L-Myc.
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U2 - 10.1038/jid.2008.365
DO - 10.1038/jid.2008.365
M3 - Article
C2 - 19020549
AN - SCOPUS:67349267297
SN - 0022-202X
VL - 129
SP - 1547
EP - 1555
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 6
ER -