Journal article
Patients with both pancreatic adenocarcinoma and melanoma may harbor germline CDKN2A mutations
Genes chromosomes & cancer, Vol.27(4), pp.358-361
04/2000
DOI: 10.1002/(SICI)1098-2264(200004)27:4<358::AID-GCC4>3.0.CO;2-O
PMID: 10719365
Abstract
Germline mutations of the CDKN2A tumor suppressor gene have been identified in melanoma kindreds linked to 9p21, and pancreatic adenocarcinoma is the second most common malignancy in some of these families. We hypothesized that unselected patients with both primary cancers, i.e., pancreatic cancer and malignant melanoma, have a genetic predisposition to tumor development, and that this susceptibility may be due to germline CDKN2A mutations. Fourteen patients, with both pathologically verified pancreatic adenocarcinoma and melanoma, were assessed for germline CDKN2A mutations by polymerase chain reaction amplification and sequencing of six overlapping fragments encompassing exons 1α and 2. A yeast two-hybrid assay was used to assess the functional consequences of CDKN2A variants. Germline CDKN2A mutations were identified in 2/14 patients: 149S, a novel substitution in exon 1α, and M531, a previously reported missense mutation in exon 2. Both variants lead to compromised CDKN2A function. We conclude that the occurrence of both pancreatic cancer and melanoma, in the same patient, signals an inherited susceptibility to cancer, and that this predisposition is, in some cases, due to germline CDKN2A mutations. This finding has important implications not only for the proband, but also for other family members. (C) 2000 Wiley-Liss, Inc.
Details
- Title: Subtitle
- Patients with both pancreatic adenocarcinoma and melanoma may harbor germline CDKN2A mutations
- Creators
- Geeta Lal - University of TorontoLing Liu - University of TorontoDavid Hogg - University of TorontoNorman J. Lassam - University of TorontoMark S. Redston - University of TorontoSteven Gallinger - University of Toronto
- Resource Type
- Journal article
- Publication Details
- Genes chromosomes & cancer, Vol.27(4), pp.358-361
- Publisher
- John Wiley & Sons, Inc
- DOI
- 10.1002/(SICI)1098-2264(200004)27:4<358::AID-GCC4>3.0.CO;2-O
- PMID
- 10719365
- ISSN
- 1045-2257
- eISSN
- 1098-2264
- Number of pages
- 4
- Language
- English
- Date published
- 04/2000
- Academic Unit
- Stead Family Department of Pediatrics; Surgery
- Record Identifier
- 9984322812702771
Metrics
7 Record Views