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PLoS Genet. 2015 Dec 18;11(12):e1005633. doi: 10.1371/journal.pgen.1005633. eCollection 2015 Dec.

Combined Genetic and Genealogic Studies Uncover a Large BAP1 Cancer Syndrome Kindred Tracing Back Nine Generations to a Common Ancestor from the 1700s.

Author information

1
Thoracic Oncology Program, University of Hawai'i Cancer Center, Honolulu, Hawai'i, United States of America.
2
Laboratory for Medical Science Mathematics, RIKEN Center for Integrative Medical Sciences, Yokohama City, Kanagawa, Japan.
3
Genealogy from the Hart, Honolulu, Hawai'i, United States of America.
4
Mesothelioma Applied Research Foundation, Alexandria, Virginia, United States of America.
5
Klinik für Thoraxchirurgie Universitätsspital, Zürich, Switzerland.
6
Department of Cardiothoracic Surgery, New York University Langone Medical Center, New York, New York, United States of America.

Abstract

We recently discovered an inherited cancer syndrome caused by BRCA1-Associated Protein 1 (BAP1) germline mutations, with high incidence of mesothelioma, uveal melanoma and other cancers and very high penetrance by age 55. To identify families with the BAP1 cancer syndrome, we screened patients with family histories of multiple mesotheliomas and melanomas and/or multiple cancers. We identified four families that shared an identical BAP1 mutation: they lived across the US and did not appear to be related. By combining family histories, molecular genetics, and genealogical approaches, we uncovered a BAP1 cancer syndrome kindred of ~80,000 descendants with a core of 106 individuals, whose members descend from a couple born in Germany in the early 1700s who immigrated to North America. Their descendants spread throughout the country with mutation carriers affected by multiple malignancies. Our data show that, once a proband is identified, extended analyses of these kindreds, using genomic and genealogical studies to identify the most recent common ancestor, allow investigators to uncover additional branches of the family that may carry BAP1 mutations. Using this knowledge, we have identified new branches of this family carrying BAP1 mutations. We have also implemented early-detection strategies that help identify cancers at early-stage, when they can be cured (melanomas) or are more susceptible to therapy (MM and other malignancies).

PMID:
26683624
PMCID:
PMC4686043
DOI:
10.1371/journal.pgen.1005633
[Indexed for MEDLINE]
Free PMC Article

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