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Neuro Oncol. 2014 Oct;16(10):1333-40. doi: 10.1093/neuonc/nou052. Epub 2014 Apr 9.

Germline rearrangements in families with strong family history of glioma and malignant melanoma, colon, and breast cancer.

Collaborators (187)

Adatto P, Morice F, Payen S, McQuinn L, McGaha R, Guerra S, Paith L, Roth K, Zeng D, Zhang H, Yung A, Aldape K, Gilbert M, Weinberger J, Colman H, Conrad C, de Groot J, Forman A, Groves M, Levin V, Loghin M, Puduvalli V, Sawaya R, Heimberger A, Lang F, Levine N, Tolentino L, Saunders K, Thach TT, Iacono DD, Sloan A, Gerson S, Selman W, Bambakidis N, Hart D, Miller J, Hoffer A, Cohen M, Rogers L, Nock CJ, Wolinsky Y, Devine K, Fulop J, Barrett W, Shimmel K, Ostrom Q, Barnett G, Rosenfeld S, Vogelbaum M, Weil R, Ahluwalia M, Peereboom D, Staugaitis S, Schilero C, Brewer C, Smolenski K, McGraw M, Naska T, Rosenfeld S, Ram Z, Blumenthal DT, Bokstein F, Umansky F, Zaaroor M, Cohen A, Tzuk-Shina T, Voldby B, Laursen R, Andersen C, Brennum J, Henriksen MB, Marzouk M, Davis ME, Boland E, Smith M, Eze O, Way M, Lada P, Miedzianowski N, Frechette M, Paleologos N, Byström G, Svedberg E, Huggert S, Kimdal M, Sandström M, Brännström N, Hayat A, Tihan T, Zheng S, Berger M, Butowski N, Chang S, Clarke J, Prados M, Rice T, Sison J, Kivett V, Duo X, Hansen H, Hsuang G, Lamela R, Ramos C, Patoka J, Wagenman K, Zhou M, Klein A, McGee N, Pfefferle J, Wilson C, Morris P, Hughes M, Britt-Williams M, Foft J, Madsen J, Polony C, McCarthy B, Zahora C, Villano J, Engelhard H, Borg A, Chanock SK, Collins P, Elston R, Kleihues P, Kruchko C, Petersen G, Plon S, Thompson P, Johansen C, Sadetzki S, Melin B, Bondy ML, Lau CC, Scheurer ME, Armstrong GN, Liu Y, Shete S, Yu RK, Aldape KD, Gilbert MR, Weinberg J, Houlston RS, Hosking FJ, Robertson L, Papaemmanuil E, Claus EB, Claus EB, Barnholtz-Sloan J, Sloan AE, Barnett G, Devine K, Wolinsky Y, Lai R, McKean-Cowdin R, Il'yasova D, Schildkraut J, Sadetzki S, Yechezkel GH, Bruchim RB, Aslanov L, Sadetzki S, Johansen C, Kosteljanetz M, Broholm H, Bernstein JL, Olson SH, Schubert E, DeAngelis L, Jenkins RB, Yang P, Rynearson A, Andersson U, Wibom C, Henriksson R, Melin BS, Cederquist K, Aradottir S, Borg A, Merrell R, Lada P, Wrensch M, Wiencke J, Wiemels J, McCoy L, McCarthy BJ, Davis FG.

Author information

Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden (U.A., C.W., B.S.M.); Computational Life Science Cluster (CLiC), Umeå University, Umeå, Sweden (C.W.); Department of Medical Biosciences, Pathology, Umeå University, Umeå Sweden (K.C.); Department of Oncology, Clinical Science, Lund University, Lund, Sweden (S.A., Å.B.); Department of Pediatrics, Section of Hematology/Oncology, Baylor College of Medicine, Houston, Texas (G.N.A., M.L.B.); Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas (S.S.); Texas Children's Cancer and Hematology Centers, Baylor College of Medicine, Houston, Texas (C.C.L.); Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas (M.N.B.); School of Public Health, Yale University, New Haven, Connecticut (E.B.C.); Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts (E.B.C.); Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio (J.B.-S.); University of Southern California, Los Angeles, California (R.L.); Cancer Control and Prevention Program/Department of Community and Family Medicine, Duke University Medical Center, Durham, North Carolina (D.I., J.S.); Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, UK (R.S.H.); Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center , New York, New York (J.L.B., S.H.O.); Mayo Comprehensive Clinic Cancer, Mayo Clinic, Rochester, Minnesota (R.B.J., D.H.L.); Department of Neurological Surgery, University of California, San Francisco, California (M.W.); School of Public Health, University of Alberta, Edmonton, Canada (F.G.D.); Department of Neurology, NorthShore University Health System, Evanston, Illinois (R.M.); Cancer Late Effects Research, Oncology, Finsencenteret, Rigshospitalet, University of Copenhagen and Head, Survivorship, Danish Cancer Society Research Center, Copenhagen, Denmark (C.J.)



Although familial susceptibility to glioma is known, the genetic basis for this susceptibility remains unidentified in the majority of glioma-specific families. An alternative approach to identifying such genes is to examine cancer pedigrees, which include glioma as one of several cancer phenotypes, to determine whether common chromosomal modifications might account for the familial aggregation of glioma and other cancers.


Germline rearrangements in 146 glioma families (from the Gliogene Consortium; were examined using multiplex ligation-dependent probe amplification. These families all had at least 2 verified glioma cases and a third reported or verified glioma case in the same family or 2 glioma cases in the family with at least one family member affected with melanoma, colon, or breast cancer.The genomic areas covering TP53, CDKN2A, MLH1, and MSH2 were selected because these genes have been previously reported to be associated with cancer pedigrees known to include glioma.


We detected a single structural rearrangement, a deletion of exons 1-6 in MSH2, in the proband of one family with 3 cases with glioma and one relative with colon cancer.


Large deletions and duplications are rare events in familial glioma cases, even in families with a strong family history of cancers that may be involved in known cancer syndromes.


CDKN2A/B; MLH1; MSH2; TP53; family history; glioma

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