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Homozygotes forCDKN2 (p16) germline mutation in Dutch familial melanoma kindreds
- Nelleke A. Gruis1,2,
- Pieter A. van der Velden1,
- Lodewijk A. Sandkuijl1,
- Duncan E. Prins1,2,
- Jane Weaver-Feldhaus3,
- Alexander Kamb3,
- Wilma Bergman2 &
- …
- Rune R. Frants1
Nature Geneticsvolume 10, pages351–353 (1995)Cite this article
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Abstract
The p16 gene (CDKN2) which is localized on chromosome 9p21, is deleted in a significant number of sporadic cancers1–3. Moreover, germline mutations identified in some melanoma-prone kindreds4,5 last year suggested thatCDKN2 is identical to the 9p21 −linked melanoma susceptibility gene (MLM)6; however, failure to identify p16 mutations in all melanoma kindreds putatively linked to 9p21 left some doubts. We have analysedCDKN2 coding sequences in 15 Dutch familial atypical multiple mole-melanoma (FAMMM) syndrome pedigrees, and identified a 19 basepair (bp) germline deletion in 13 of them. All 13 families originate from an endogamous population. The deletion causes a reading frame shift, predicted to result in a severely truncated p16 protein. Interestingly, two family members are homozygous for the deletion, one of whom shows no obvious signs of disease. This surprising finding demonstrates that homozygotes for thisCDKN2 mutation are viable, and suggests the presence of a genetic mechanism that can compensate for the functional loss of p16. Our results also greatly strengthen the notion that p16 is indeedMLM.
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Authors and Affiliations
MGC-Department of Human Genetics, Leiden University, The Netherlands
Nelleke A. Gruis, Pieter A. van der Velden, Lodewijk A. Sandkuijl, Duncan E. Prins & Rune R. Frants
Department of Dermatology, University Hospital Leiden, The Netherlands
Nelleke A. Gruis, Duncan E. Prins & Wilma Bergman
Myriad Genetics Inc., Salt Lake City, Utah, USA
Jane Weaver-Feldhaus & Alexander Kamb
- Nelleke A. Gruis
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- Pieter A. van der Velden
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- Lodewijk A. Sandkuijl
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- Duncan E. Prins
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- Jane Weaver-Feldhaus
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- Alexander Kamb
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- Wilma Bergman
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- Rune R. Frants
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Gruis, N., van der Velden, P., Sandkuijl, L.et al. Homozygotes forCDKN2 (p16) germline mutation in Dutch familial melanoma kindreds.Nat Genet10, 351–353 (1995). https://doi.org/10.1038/ng0795-351
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