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Novel germline p16 mutation in familial malignant melanoma in southern Sweden

Borg, Åke LU ; Johannsson, U; Johannsson, O LU ; Hakansson, Sara; Westerdahl, J LU ; Mäsbäck, A LU ; Olsson, Håkan LU and Ingvar, C LU (1996) In Cancer Research 56(11). p.500-2497
Abstract

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... (More)

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.

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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
in
Cancer Research
volume
56
issue
11
pages
4 pages
publisher
American Association for Cancer Research Inc.
external identifiers
  • scopus:0029891364
ISSN
0008-5472
language
English
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yes
id
c892fccf-b5e1-423c-9abf-d86fe39a95f3
date added to LUP
2016-09-18 12:51:39
date last changed
2017-05-28 04:52:17
@article{c892fccf-b5e1-423c-9abf-d86fe39a95f3,
  abstract     = {<p>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.</p>},
  author       = {Borg, Åke and Johannsson, U and Johannsson, O and Hakansson, Sara and Westerdahl, J and Mäsbäck, A and Olsson, Håkan and Ingvar, C},
  issn         = {0008-5472},
  keyword      = {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},
  language     = {eng},
  month        = {06},
  number       = {11},
  pages        = {500--2497},
  publisher    = {American Association for Cancer Research Inc.},
  series       = {Cancer Research},
  title        = {Novel germline p16 mutation in familial malignant melanoma in southern Sweden},
  volume       = {56},
  year         = {1996},
}