Heterozygous Germ Line hCHK2 Mutations in Li-Fraumeni Syndrome-Reference-Cited by-同舟云学术

Heterozygous Germ Line hCHK2 Mutations in Li-Fraumeni Syndrome

Published:1999-12-24 Issue:5449 Volume:286 Page:2528-2531
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Bell Daphne W.¹,Varley Jennifer M.²,Szydlo Tara E.¹,Kang Deborah H.¹,Wahrer Doke C. R.¹,Shannon Kristen E.¹,Lubratovich Marcie¹,Verselis Sigitas J.³,Isselbacher Kurt J.¹,Fraumeni Joseph F.⁴,Birch Jillian M.⁵,Li Frederick P.³,Garber Judy E.³,Haber Daniel A.¹

Affiliation:

1. Massachusetts General Hospital Center for Cancer Risk Analysis and Harvard Medical School, Building 149, Charlestown, MA 02129, USA.

2. Cancer Research Campaign Department of Cancer Genetics, Paterson Institute for Cancer Research, Manchester M20 4BX, UK.

3. Division of Population Sciences, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02114, USA.

4. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

5. Cancer Research Campaign Paediatric and Familial Cancer Research Group, Royal Manchester Children's Hospital, Manchester M27 1HA, UK.

Abstract

The hCHK2 gene encodes the human homolog of the yeast Cds1 and Rad53 G 2 checkpoint kinases, whose activation in response to DNA damage prevents cellular entry into mitosis. Here, it is shown that heterozygous germ line mutations in hCHK2 occur in Li-Fraumeni syndrome, a highly penetrant familial cancer phenotype usually associated with inherited mutations in the TP53 gene. These observations suggest that hCHK2 is a tumor suppressor gene conferring predisposition to sarcoma, breast cancer, and brain tumors, and they also provide a link between the central role of p53 inactivation in human cancer and the well-defined G 2 checkpoint in yeast.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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