title: Phenotypic variation in eight extended CDKN2A germline mutation familial atypical multiple mole melanoma-pancreatic carcinoma-prone families: the familial atypical mole melanoma-pancreatic carcinoma syndrome.
abstract: BACKGROUND
  Hereditary pancreatic carcinoma shows extant phenotypic and genotypic heterogeneity as evidenced by its integral association with a variety of hereditary cancer syndromes inclusive of the familial atypical multiple mole melanoma (FAMMM) syndrome in concert with CDKN2A (p16) germline mutations.
  
  
  METHODS
  Creighton University's familial pancreatic carcinoma resource comprises 159 families of which 19 (12%) show the FAMMM cutaneous phenotypes. The authors describe eight families with the FAMMM-pancreatic carcinoma (FAMMM-PC) association in concert with a CDKN2A germline mutation. Each family was thoroughly educated about all facets of the study, including the molecular genetics, reduced penetrance of CDKN2A mutations, and their variable expressivity. Genetic counseling was provided to each patient.
  
  
  RESULTS
  Diversity in cancer presentation within and among the families was noteworthy, wherein melanoma predominated in certain of the families whereas pancreatic carcinoma predominated in others. Early-onset pancreatic carcinoma (at ages 35, 45, 46, and 49 years) appeared in some of the families whereas markedly later-onset pancreatic carcinoma occurred in others. There were four incidences of melanoma and pancreatic carcinoma as double primaries in the same individuals. One patient with melanoma and pancreatic carcinoma had a third primary of breast carcinoma. Another patient had sarcoma, esophageal carcinoma, and two melanoma primaries, whereas his daughter had sarcoma and was a carrier of a CDKN2A mutation.
  
  
  CONCLUSIONS
  The authors suggest that these tumors may collectively, in concert with CDKN2A mutations, constitute a "new" putative hereditary carcinoma syndrome referred to as FAMMM-PC. More clinical and molecular genetic research on additional families with pancreatic carcinoma in concert with the FAMMM will be required.
authors.affiliation: Department of Preventive Medicine, Creighton University School of Medicine, Omaha, Nebraska 68178, USA. trlynch@creighton.edu
authors.forename: Henry T
authors.initials: HT
authors.lastname: Lynch
authors.forename: Randall E
authors.initials: RE
authors.lastname: Brand
authors.forename: David
authors.initials: D
authors.lastname: Hogg
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Deters
authors.forename: Ramon M
authors.initials: RM
authors.lastname: Fusaro
authors.forename: Jane F
authors.initials: JF
authors.lastname: Lynch
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.forename: Joseph
authors.initials: J
authors.lastname: Knezetic
authors.forename: Norman J
authors.initials: NJ
authors.lastname: Lassam
authors.forename: Michael
authors.initials: M
authors.lastname: Goggins
authors.forename: Scott
authors.initials: S
authors.lastname: Kern
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D004416:Dysplastic Nevus Syndrome / Q000235:genetics* / Q000473:pathology; D005260:Female; D019942:Genes, p16; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009386:Neoplastic Syndromes, Hereditary / Q000145:classification / Q000235:genetics / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology