Allelic imbalances and microdeletions affecting the PTPRD gene in cutaneous squamous cell carcinomas detected using single nucleotide polymorphism microarray analysis
- 9 April 2007
- journal article
- research article
- Published by Wiley in Genes, Chromosomes and Cancer
- Vol. 46 (7), 661-669
- https://doi.org/10.1002/gcc.20447
Abstract
Cutaneous squamous cell carcinomas (SCC) are the second most commonly diagnosed cancers in fair‐skinned people; yet the genetic mechanisms involved in SCC tumorigenesis remain poorly understood. We have used single nucleotide polymorphism (SNP) microarray analysis to examine genome‐wide allelic imbalance in 16 primary and 2 lymph node metastatic SCC using paired non‐tumour samples to counteract normal copy number variation. The most common genetic change was loss of heterozygosity (LOH) on 9p, observed in 13 of 16 primary SCC. Other recurrent events included LOH on 3p (9 tumors), 2q, 8p, and 13 (each in 8 SCC) and allelic gain on 3q and 8q (each in 6 tumors). Copy number‐neutral LOH was observed in a proportion of samples, implying that somatic recombination had led to acquired uniparental disomy, an event not previously demonstrated in SCC. As well as recurrent patterns of gross chromosomal changes, SNP microarray analysis revealed, in 2 primary SCC, a homozygous microdeletion on 9p23 within the protein tyrosine phosphatase receptor type D (PTPRD) locus, an emerging frequent target of homozygous deletion in lung cancer and neuroblastoma. A third sample was heterozygously deleted within this locus and PTPRD expression was aberrant. Two of the 3 primary SCC with PTPRD deletion had demonstrated metastatic potential. Our data identify PTPRD as a candidate tumor suppressor gene in cutaneous SCC with a possible association with metastasis.Keywords
This publication has 27 references indexed in Scilit:
- Global variation in copy number in the human genomeNature, 2006
- The Consensus Coding Sequences of Human Breast and Colorectal CancersScience, 2006
- Are Keratoacanthomas Variants of Squamous Cell Carcinomas? A Comparison of Chromosomal Aberrations by Comparative Genomic HybridizationJournal of Investigative Dermatology, 2006
- Association between Acquired Uniparental Disomy and Homozygous Gene Mutation in Acute Myeloid LeukemiasCancer Research, 2005
- Genomewide Single Nucleotide Polymorphism Microarray Mapping in Basal Cell Carcinomas Unveils Uniparental Disomy as a Key Somatic EventCancer Research, 2005
- Identification of chromosome arm 9p as the most frequent target of homozygous deletions in lung cancerGenes, Chromosomes and Cancer, 2005
- Predictions of skin cancer incidence in the Netherlands up to 2015British Journal of Dermatology, 2005
- Restoration of receptor-type protein tyrosine phosphatase function inhibits human pancreatic carcinoma cell growth in vitro and in vivoCarcinogenesis: Integrative Cancer Research, 2004
- p16INK4a and p14ARF Tumor Suppressor Genes Are Commonly Inactivated in Cutaneous Squamous Cell CarcinomaJournal of Investigative Dermatology, 2004
- P16 UV mutations in human skin epithelial tumorsOncogene, 1999