title: Metastatic cutaneous squamous cell carcinoma shows frequent deletion in the protein tyrosine phosphatase receptor Type D gene.
abstract: Cutaneous squamous cell carcinoma (cSCC) is the second most common form of nonmelanoma skin cancer (NMSC), and its incidence is increasing rapidly. Metastatic cSCC accounts for the majority of deaths associated with NMSC, but the genetic basis for cSCC progression remains poorly understood. A previous study identified small deletions (typically <1 Mb) in the protein tyrosine phosphatase receptor Type D (PTPRD) gene that segregated with more aggressive cSCC. To investigate the apparent association between deletion within PTPRD and cSCC metastasis, a series of 74 formalin-fixed paraffin-embedded tumors from 31 patients was analyzed using a custom Illumina 384 SNP microarray. Deletions were found in 37% of patients with metastatic cSCC and were strongly associated with metastatic tumors when compared to those that had not metastasized (p = 0.007). Subsequent mutation analysis revealed a higher mutation rate for PTPRD than has been reported in any other cancer type, with 37% of tumors harboring a somatic mutation. Conversely, bisulfite sequencing showed that methylation was not a mechanism of PTPRD disruption in cSCC. This is the first report to observe an association between deletion within PTPRD and metastatic disease and highlights the potential use of these deletions as a diagnostic biomarker for tumor progression. Combined with the high mutation rate observed in our study, PTPRD is one of the most commonly altered genes in cSCC and warrants further investigation to determine its significance for metastasis in other tumor types.
authors: Centre for Cutaneous Research, Blizard Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry, Queen Mary, University of London, London, United Kingdom. sl575@cam.ac.uk
authors: Sally R
authors: SR
authors: Lambert
authors: Catherine A
authors: CA
authors: Harwood
authors: Karin J
authors: KJ
authors: Purdie
authors: Abha
authors: A
authors: Gulati
authors: Rubeta N
authors: RN
authors: Matin
authors: Malgorzata
authors: M
authors: Romanowska
authors: Rino
authors: R
authors: Cerio
authors: David P
authors: DP
authors: Kelsell
authors: Irene M
authors: IM
authors: Leigh
authors: Charlotte M
authors: CM
authors: Proby
mesh_terms: D001483:Base Sequence; D014408:Biomarkers, Tumor; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D018450:Disease Progression; D005838:Genotype; D006801:Humans; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D016612:Paraffin Embedding; D020641:Polymorphism, Single Nucleotide; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C090899:PTPRD protein, human; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2