title: Allelic imbalances and microdeletions affecting the PTPRD gene in cutaneous squamous cell carcinomas detected using single nucleotide polymorphism microarray analysis.
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.
authors.affiliation: Cancer Research UK Skin Tumour Laboratory, Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry, Queen Mary, University of London, London, England, UK. k.purdie@qmul.ac.uk
authors.forename: Karin J
authors.initials: KJ
authors.lastname: Purdie
authors.forename: Sally R
authors.initials: SR
authors.lastname: Lambert
authors.forename: Muy-Teck
authors.initials: MT
authors.lastname: Teh
authors.forename: Tracy
authors.initials: T
authors.lastname: Chaplin
authors.forename: Gael
authors.initials: G
authors.lastname: Molloy
authors.forename: Manoj
authors.initials: M
authors.lastname: Raghavan
authors.forename: David P
authors.initials: DP
authors.lastname: Kelsell
authors.forename: Irene M
authors.initials: IM
authors.lastname: Leigh
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Harwood
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Proby
authors.forename: Bryan D
authors.initials: BD
authors.lastname: Young
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002869:Chromosome Aberrations; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2; D012878:Skin Neoplasms / Q000235:genetics*
chemical_list: C090899:PTPRD protein, human; D017027:Protein Tyrosine Phosphatases; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2