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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.

SUBMITTER: Grant RC

PROVIDER: S-EPMC3639869 | biostudies-other | 2013 Apr

REPOSITORIES: biostudies-other

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Exome sequencing identifies nonsegregating nonsense ATM and PALB2 variants in familial pancreatic cancer.

Grant Robert C RC Al-Sukhni Wigdan W Borgida Ayelet E AE Holter Spring S Kanji Zaheer S ZS McPherson Treasa T Whelan Emily E Serra Stefano S Trinh Quang M QM Peltekova Vanya V Stein Lincoln D LD McPherson John D JD Gallinger Steven S

Human genomics 20130405

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 sequen ...[more]

PMID: 23561644

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