Germline Mutations in Shelterin Complex Genes Are Associated With Familial Glioma

被引：161

作者：

Bainbridge, Matthew N. ^{[1
,2
]}

Armstrong, Georgina N. ^{[3
]}

Gramatges, M. Monica ^{[3
]}

Bertuch, Alison A. ^{[3
]}

Jhangiani, Shalini N. ^{[1
]}

Doddapaneni, Harsha ^{[1
]}

Lewis, Lora ^{[1
]}

Tombrello, Joseph ^{[1
]}

Tsavachidis, Spyros ^{[3
]}

Liu, Yanhong ^{[3
]}

Jalali, Ali ^{[4
]}

Plon, Sharon E. ^{[3
]}

Lau, Ching C. ^{[3
]}

Parsons, Donald W. ^{[3
]}

Claus, Elizabeth B. ^{[5
,6
]}

Barnholtz-Sloan, Jill ^{[7
]}

Il'yasova, Dora ^{[8
,9
]}

Schildkraut, Joellen ^{[9
]}

Ali-Osman, Francis ^{[10
]}

Sadetzki, Siegal ^{[11
,12
]}

Johansen, Christoffer ^{[13
]}

Houlston, Richard S. ^{[14
]}

Jenkins, Robert B. ^{[15
]}

Lachance, Daniel ^{[15
]}

Olson, Sara H. ^{[16
]}

Bernstein, Jonine L. ^{[16
]}

Merrell, Ryan T. ^{[17
]}

Wrensch, Margaret R. ^{[18
]}

Walsh, Kyle M. ^{[18
]}

Davis, Faith G. ^{[19
]}

Lai, Rose ^{[20
,21
,22
]}

Shete, Sanjay ^{[23
]}

Aldape, Kenneth ^{[24
]}

Amos, Christopher I. ^{[25
]}

Thompson, Patricia A. ^{[26
]}

Muzny, Donna M. ^{[1
]}

Gibbs, Richard A. ^{[1
]}

Melin, Beatrice S. ^{[27
]}

Bondy, Melissa L. ^{[3
]}

机构：

[1] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA

[2] Codified Genom LLC, Houston, TX USA

[3] Baylor Coll Med, Dan L Duncan Canc Ctr, Div Hematol Oncol, Dept Pediat, Houston, TX 77030 USA

[4] Baylor Coll Med, Dept Neurosurg, Houston, TX 77030 USA

[5] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA

[6] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA

[7] Case Western Reserve Univ, Sch Med, Case Comprehens Canc Ctr, Cleveland, OH USA

[8] Georgia State Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Atlanta, GA 30303 USA

[9] Duke Univ, Med Ctr, Dept Community & Family Med, Canc Control & Prevent Program, Durham, NC 27710 USA

[10] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA

[11] Chaim Sheba Med Ctr, Gertner Inst, Canc & Radiat Epidemiol Unit, IL-52621 Tel Hashomer, Israel

[12] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel

[13] Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark

[14] Inst Canc Res, Sect Canc Genet, Sutton, Surrey, England

[15] Mayo Clin, Mayo Clin Comprehens Canc Ctr, Rochester, MN USA

[16] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA

[17] NorthShore Univ Hlth Syst, Dept Neurol, Evanston, IL USA

[18] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA

[19] Univ Alberta, Dept Publ Hlth Serv, Edmonton, AB, Canada

[20] Univ So Calif, Keck Sch Med, Dept Neurol, Los Angeles, CA 90033 USA

[21] Univ So Calif, Keck Sch Med, Dept Neurosurg, Los Angeles, CA 90033 USA

[22] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA

[23] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA

[24] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA

[25] Geisel Sch Med Dartmouth, Norris Cotton Canc Ctr, Dept Genet, Dept Community & Family Med, Hanover, NH USA

[26] Univ Arizona, Ctr Canc, Dept Cellular & Mol Med, Tucson, AZ USA

[27] Umea Univ, Dept Radiat Sci Oncol, Umea, Sweden

来源：

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE | 2015年 / 107卷 / 01期

基金：

美国国家卫生研究院;

关键词：

TELOMERE LENGTH; POT1; RISK; CANCER; PREDISPOSE; CONSORTIUM; VARIANTS; GLIOGENE; MELANOMA; PROTEIN;

D O I：

10.1093/jnci/dju384

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Gliomas are the most common brain tumor, with several histological subtypes of various malignancy grade. The genetic contribution to familial glioma is not well understood. Using whole exome sequencing of 90 individuals from 55 families, we identified two families with mutations in POT1 (p.G95C, p.E450X), a member of the telomere shelterin complex, shared by both affected individuals in each family and predicted to impact DNA binding and TPP1 binding, respectively. Validation in a separate cohort of 264 individuals from 246 families identified an additional mutation in POT1 (p.D617Efs), also predicted to disrupt TPP1 binding. All families with POT1 mutations had affected members with oligodendroglioma, a specific subtype of glioma more sensitive to irradiation. These findings are important for understanding the origin of glioma and could have importance for the future diagnostics and treatment of glioma.

引用

页数：4

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