title: Array-CGH reveals recurrent genomic changes in Merkel cell carcinoma including amplification of L-Myc.
abstract: 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 (P=0.04). 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 4/4 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.
authors.affiliation: Department of Medicine, University of Washington, Seattle, Washington 98109, USA.
authors.forename: Kelly G
authors.initials: KG
authors.lastname: Paulson
authors.forename: Bianca D
authors.initials: BD
authors.lastname: Lemos
authors.forename: Bin
authors.initials: B
authors.lastname: Feng
authors.forename: Natalia
authors.initials: N
authors.lastname: Jaimes
authors.forename: Pablo F
authors.initials: PF
authors.lastname: Peñas
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Bi
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Maher
authors.forename: Lisa
authors.initials: L
authors.lastname: Cohen
authors.forename: J Helen
authors.initials: JH
authors.lastname: Leonard
authors.forename: Scott R
authors.initials: SR
authors.lastname: Granter
authors.forename: Lynda
authors.initials: L
authors.lastname: Chin
authors.forename: Paul
authors.initials: P
authors.lastname: Nghiem
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015266:Carcinoma, Merkel Cell / Q000235:genetics*; D045744:Cell Line, Tumor; D002874:Chromosome Mapping; D055028:Comparative Genomic Hybridization; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D012008:Recurrence; D012878:Skin Neoplasms / Q000378:metabolism*; D055752:Small Cell Lung Carcinoma / Q000235:genetics*
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc