Genetic susceptibility to Melanoma 5-10% of individuals who develop melanoma show an affected close relative


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Genetic susceptibility to Melanoma

  • 5-10% of individuals who develop melanoma show an affected close relative

  • Susceptibility to melanoma is inherited as an autosomal dominant trait, with a incomplete penetrance













MAPK PATHWAY

  • In contrast to BRAF mutations, NRAS alterations are more common in sun-exposed areas

  • HRAS mutations are less commonly observed and occurs in no more than 1.5-3% of melanomas

  • Activating changes in KRAS2 have been observed in rare cases and often associated with other

  • Ras genes mutations









PTEN (10q23.31)

  • PTEN (10q23.31)



CDKN2A germline mutations in familial melanoma

  • Identified in 15-20% of melanoma-prone families (at least two affected first or second degree relatives)

  • Present in 9-15 % of

  • sporadic multiple primary melanomas (MPM)

  • Penetrance of 53% by age 80

  • Interaction with sunlight exposure

  • High frequency of multiple primary melanomas (MPM), pancreatic and larynx cancer



















CDKN2A 1β (p14ARF): worldwide mutations

  • Locus Base Nr of geneal. Origin

  • g.192 A>T 1 UK

  • g.193 G>C 1 UK

  • g.193+1 G>A 1 Netherland

  • g.193+2 T>C 1 USA

  • g.193+3 A>G 1 UK

  • g.193+56 T>C 2 UK

























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