Andersson Ulrika, Wibom Carl, Cederquist Kristina, Aradottir Steina, Borg Ake, Armstrong Georgina N, Shete Sanjay, Lau Ching C, Bainbridge Matthew N, Claus Elizabeth B, Barnholtz-Sloan Jill, Lai Rose, Il'yasova Dora, Houlston Richard S, Schildkraut Joellen, Bernstein Jonine L, Olson Sara H, Jenkins Robert B, Lachance Daniel H, Wrensch Margaret, Davis Faith G, Merrell Ryan, Johansen Christoffer, Sadetzki Siegal, Bondy Melissa L, Melin Beatrice S
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.)
Neuro Oncol. 2014 Oct;16(10):1333-40. doi: 10.1093/neuonc/nou052. Epub 2014 Apr 9.
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; http://www.gliogene.org/) 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.
尽管已知胶质瘤存在家族易感性，但在大多数特定于胶质瘤的家族中，这种易感性的遗传基础仍未明确。另一种识别此类基因的方法是研究癌症家系，这些家系将胶质瘤作为几种癌症表型之一，以确定常见的染色体改变是否可能解释胶质瘤和其他癌症的家族聚集现象。
使用多重连接依赖探针扩增技术检测了146个胶质瘤家族（来自Gliogene联盟；http://www.gliogene.org/）的种系重排。这些家族均至少有2例经证实的胶质瘤病例，且在同一家族中有第三例报告或经证实的胶质瘤病例，或者家族中有2例胶质瘤病例，且至少有一名家庭成员患有黑色素瘤、结肠癌或乳腺癌。选择覆盖TP53、CDKN2A、MLH1和MSH2的基因组区域，因为这些基因先前已被报道与已知包括胶质瘤的癌症家系相关。
在一个有3例胶质瘤病例和1例结肠癌亲属的家族的先证者中，我们检测到一个单一的结构重排，即MSH2外显子1 - 6的缺失。
在家族性胶质瘤病例中，大的缺失和重复是罕见事件，即使在有很强癌症家族史且可能涉及已知癌症综合征的家族中也是如此。
