title: Exome sequencing identifies nonsegregating nonsense ATM and PALB2 variants in familial pancreatic cancer.
abstract: We sequenced 11 germline exomes from five families with familial pancreatic cancer (FPC). One proband had a germline nonsense variant in ATM with somatic loss of the variant allele. Another proband had a nonsense variant in PALB2 with somatic loss of the variant allele. Both variants were absent in a relative with FPC. These findings question the causal mechanisms of ATM and PALB2 in these families and highlight challenges in identifying the causes of familial cancer syndromes using exome sequencing.
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, M5G 1X5, Canada.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Grant
authors.forename: Wigdan
authors.initials: W
authors.lastname: Al-Sukhni
authors.forename: Ayelet E
authors.initials: AE
authors.lastname: Borgida
authors.forename: Spring
authors.initials: S
authors.lastname: Holter
authors.forename: Zaheer S
authors.initials: ZS
authors.lastname: Kanji
authors.forename: Treasa
authors.initials: T
authors.lastname: McPherson
authors.forename: Emily
authors.initials: E
authors.lastname: Whelan
authors.forename: Stefano
authors.initials: S
authors.lastname: Serra
authors.forename: Quang M
authors.initials: QM
authors.lastname: Trinh
authors.forename: Vanya
authors.initials: V
authors.lastname: Peltekova
authors.forename: Lincoln D
authors.initials: LD
authors.lastname: Stein
authors.forename: John D
authors.initials: JD
authors.lastname: McPherson
authors.forename: Steven
authors.initials: S
authors.lastname: Gallinger
mesh_terms: D000483:Alleles; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics*; D001483:Base Sequence; D002277:Carcinoma / Q000235:genetics*; D020090:Chromosome Segregation / Q000235:genetics*; D018389:Codon, Nonsense / Q000235:genetics*; D059472:Exome / Q000235:genetics*; D000076164:Fanconi Anemia Complementation Group N Protein; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics*; D010375:Pedigree; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D000076164:Fanconi Anemia Complementation Group N Protein; D009687:Nuclear Proteins; C512790:PALB2 protein, human; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins
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