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

Robert C Grant1, Wigdan Al-Sukhni12, Ayelet E Borgida3, Spring Holter3, Zaheer S Kanji1, Treasa McPherson1, Emily Whelan1, Stefano Serra4, Quang M Trinh5, Vanya Peltekova5, Lincoln D Stein5, John D McPherson5 and Steven Gallinger1236*

Author Affiliations

1 Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, M5G 1X5, Canada

2 Division of General Surgery, Hepatobiliary/Pancreatic Surgical Oncology Program, Department of Surgery, University Health Network, University of Toronto, Toronto, M5S 3J3, Canada

3 Zane Cohen Centre for Digestive Diseases Clinical Research Centre, Mount Sinai Hospital, Toronto, M5T 3L9, Canada

4 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, M5S 1A1, Canada

5 Ontario Institute for Cancer Research, Toronto, M5G 1L7, Canada

6 Toronto General Hospital, 10EN206, 200 Elizabeth Street, Toronto, ON, M5G 2C4, Canada

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Human Genomics 2013, 7:11  doi:10.1186/1479-7364-7-11

Published: 5 April 2013


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.

Hereditary cancer; Pancreas cancer; Germline variants; Genetic counseling; Carcinogenesis