Intronic sequence variants of theCDKN2A gene in melanoma pedigrees
| Autor: | Claire Taylor, Sylvia Bass, D. Timothy Bishop, Juliette Randerson-Moor, Mark Harland, Julia A. Newton Bishop, Graham J. Mann, Elizabeth A. Holland, Michael Churchman |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Cancer Research RNA Splicing Population Pedigree chart Biology Germline mutation CDKN2A Genetics Intronic Mutation Humans education Melanoma neoplasms Gene Germ-Line Mutation DNA Primers education.field_of_study Base Sequence Reverse Transcriptase Polymerase Chain Reaction Genes p16 Intron Introns Pedigree stomatognathic diseases RNA splicing Female |
| Zdroj: | Genes, Chromosomes and Cancer. 43:128-136 |
| ISSN: | 1098-2264 1045-2257 |
| DOI: | 10.1002/gcc.20177 |
| Popis: | Germ-line mutations of the tumor-suppressor gene CDKN2A predispose individuals to melanoma in families worldwide. However, coding mutations of CDKN2A have not been detected in a significant proportion of those affected. The identification of a disease-associated intronic mutation of CDKN2A in UK families, which has proved to be the most common CDKN2A mutation as yet identified in this population, has highlighted the possibility that additional causal mutations may lie within the intronic sequence of the gene. In this article, we describe the comprehensive screening of 109 English and 26 Australian melanoma pedigrees for intronic mutations of CDKN2A. In total, 24 sequence variants were identified across the two introns of the gene. We show evidence that two of the CDKN2A intronic variants (IVS1 + 1104 C > A and IVS1 - 1104 C > G) predispose to melanoma. IVS1 + 1104 was shown to result in the aberrant splicing of both p16(INK4a) and p14(ARF) mRNA. Overall, however, the proportion of English melanoma families with these variants is small. |
| Databáze: | OpenAIRE |
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