Melanoma-pancreatic cancer syndrome is an inherited cancer predisposition syndrome in which mutation carriers have an increased risk of developing malignant melanoma and/or pancreatic cancer. Mutation carriers within families may develop either or both types of cancer (summary by ... Melanoma-pancreatic cancer syndrome is an inherited cancer predisposition syndrome in which mutation carriers have an increased risk of developing malignant melanoma and/or pancreatic cancer. Mutation carriers within families may develop either or both types of cancer (summary by Harinck et al., 2012). For background and phenotypic information on malignant melanoma and pancreatic cancer, see 155600 and 260350, respectively.
Whelan et al. (1995) described a kindred with an increased risk of pancreatic cancers, melanomas, and possibly additional types of tumors cosegregating with the CDKN2A gly93-to-trp mutation (G93W; 600160.0005). Of interest was the occurrence of squamous-cell carcinomas in ... Whelan et al. (1995) described a kindred with an increased risk of pancreatic cancers, melanomas, and possibly additional types of tumors cosegregating with the CDKN2A gly93-to-trp mutation (G93W; 600160.0005). Of interest was the occurrence of squamous-cell carcinomas in this family, a rare form, and squamous cell carcinoma of the tongue in the proband. Goldstein et al. (1995) also showed that pancreatic carcinoma was found within melanoma families in individuals carrying CDKN2A mutations. Schutte et al. (1997) showed that almost all pancreatic carcinomas have inactivation of the CDKN2A gene. Vasen et al. (2000) performed mutation analysis on 27 families with FAMMM syndrome and identified the CDKN2A-Leiden mutation (600160.0003) in 19 families. They identified 86 patients with melanoma, and the second most frequent cancer was pancreatic carcinoma, which was observed in 15 patients from 7 families. The mean age at diagnosis of pancreatic carcinoma was 58 years, with a range from 38 to 77 years. Putative mutation carriers had an estimated cumulative risk of 17% for developing pancreatic carcinoma by age 75 years. In the 8 CDKN2A-Leiden-negative families, no cases of pancreatic carcinoma had occurred. The authors concluded that individuals with the CDKN2A-Leiden mutation show an enormous risk of developing pancreatic cancer. Lynch et al. (2002) described 8 families with what they termed the FAMMMPC syndrome who had mutations in the CDKN2A gene. They stated that the Creighton University registry of familial pancreatic cancer had 159 families, of which 19 (12%) showed the FAMMM cutaneous phenotype. Harinck et al. (2012) identified CDKN2A mutations in 6 (21%) of 28 families ascertained for familial clustering of pancreatic cancer. Five of the 6 families were of Caucasian origin and carried the same Dutch founder mutation (19-bp del; 600160.0003). Four of the 5 families with the Leiden mutation had members who developed melanoma. In the fifth family, only pancreatic cancer segregated with mutation status. A sixth family, of Indonesian origin, with only pancreatic cancer and no melanoma carried a different heterozygous mutation in the CDKN2A gene (600160.0022). Harinck et al. (2012) concluded that the CDKN2A gene should be analyzed in families with pancreatic cancer, even if melanoma is not present.
In a population-based study, Ghiorzo et al. (2012) identified CDKN2A mutations in 13 (5.7%) of 225 Italian patients with pancreatic cancer. Six patients carried the common G101W mutation (600160.0005), which was the most common mutation. Among the 16 ... In a population-based study, Ghiorzo et al. (2012) identified CDKN2A mutations in 13 (5.7%) of 225 Italian patients with pancreatic cancer. Six patients carried the common G101W mutation (600160.0005), which was the most common mutation. Among the 16 probands with a family history of cancer, including pancreatic cancer and melanoma, 5 (31%) were found to carry CDKN2A mutations. The mutation frequency ranged from 20% in families with 2 affected members to 50% in families with 3 affected members. The findings suggested that CDKN2A is the main susceptibility gene in Italian families with pancreatic cancer.