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CDKN2A germline splicing mutation affecting both p16 ink4 and p14 arf RNA processing in a melanoma/neurofibroma kindred
Author(s) -
Petronzelli Fiorella,
Sollima Danila,
Coppola Giuseppe,
MartiniNeri Maria Enrica,
Neri Giovanni,
Genuardi Maurizio
Publication year - 2001
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.1159
Subject(s) - cdkn2a , biology , exon , genetics , locus (genetics) , germline mutation , missense mutation , cancer research , melanoma , nonsense mutation , rna splicing , germline , allele , rna , microbiology and biotechnology , mutation , gene
The CDKN2A locus encodes two tumor suppressor proteins, p16 ink4 and p14 arf , through use of alternative first exons. CDKN2A mutations detected in melanoma families are usually missense or nonsense changes which mainly impair p16 ink4 function. Large genomic deletions spanning the entire locus have been observed in two pedigrees with melanomas and nervous tumors. We have detected a novel splice site mutation in a family with melanomas, neurofibromas, and multiple dysplastic nevi. Both alternative mRNAs produced by the mutant allele lacked shared sequences from exon 2, which encodes a substantial portion (>50%) of both p16 ink4 and p14 arf proteins. The development of neurofibromas can be explained by cooperative effects of combined inactivation of p16 ink4 and p14 arf or, alternatively, of p14 arf alone. © 2001 Wiley‐Liss, Inc.