Åke Borg
Principal investigator
Novel germline p16 mutation in familial malignant melanoma in southern Sweden
Author
Summary, in English
The p16 (CDKN2/MTS1/INK4a) malignant melanoma susceptibility gene was analyzed in 10 melanoma kindreds from southern Sweden using single-stranded conformation polymorphism analysis of all three exons and flanking intron regions followed by sequence analysis. A novel germline mutation, constituting an in-frame 3-bp duplication at nucleotide 332 in exon 2, was identified in two families (Lund M2 and M9). The mutation results in an insertion of Arg at codon 105, which interrupts the last of the four ankyrin repeats of the p16 protein, motifs which have been demonstrated as important in binding and inhibiting the activity of cyclin D-dependent kinases 4 and 6 in cell cycle G1 phase regulation. All five tested individuals of Lund M2 and M9 affected by melanoma were mutation carriers, as were five melanoma-free individuals. Other malignancies observed in gene carriers or obligate carriers included cervical, breast, and pancreatic carcinomas and a non-Hodgkin's lymphoma. Analysis of microsatellite markers adjacent to the p16 gene at chromosomal region 9p21 revealed that both families share a common haplotype, in keeping with a common ancestor.
Department/s
- Breastcancer-genetics
- Surgery (Lund)
- Tumor microenvironment
- Medical oncology
- Lund Melanoma Study Group
Publishing year
1996-06-01
Language
English
Pages
500-2497
Publication/Series
Cancer Research
Volume
56
Issue
11
Document type
Journal article
Publisher
American Association for Cancer Research Inc.
Topic
- Cancer and Oncology
Keywords
- Carrier Proteins
- Chromosomes, Human, Pair 9
- Cyclin-Dependent Kinase Inhibitor p16
- Female
- Genes
- Genes, Tumor Suppressor
- Humans
- Male
- Melanoma
- Pedigree
- Point Mutation
- Polymorphism, Single-Stranded Conformational
- Sweden
Status
Published
Research group
- Lund Melanoma Study Group
ISBN/ISSN/Other
- ISSN: 0008-5472