title: Targeted sequencing in chromosome 17q linkage region identifies familial glioma candidates in the Gliogene Consortium.
abstract: Glioma is a rare, but highly fatal, cancer that accounts for the majority of malignant primary brain tumors. Inherited predisposition to glioma has been consistently observed within non-syndromic families. Our previous studies, which involved non-parametric and parametric linkage analyses, both yielded significant linkage peaks on chromosome 17q. Here, we use data from next generation and Sanger sequencing to identify familial glioma candidate genes and variants on chromosome 17q for further investigation. We applied a filtering schema to narrow the original list of 4830 annotated variants down to 21 very rare (<0.1% frequency), non-synonymous variants. Our findings implicate the MYO19 and KIF18B genes and rare variants in SPAG9 and RUNDC1 as candidates worthy of further investigation. Burden testing and functional studies are planned.
authors: Department of Neurosurgery, Baylor College of Medicine, Houston, Texas.
authors: Ali
authors: A
authors: Jalali
authors: Department of Pediatrics, Division of Hematology-Oncology, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas.
authors: E Susan
authors: ES
authors: Amirian
authors: 1] Codified Genomics, LLC, Houston Texas [2] Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas.
authors: Matthew N
authors: MN
authors: Bainbridge
authors: Department of Pediatrics, Division of Hematology-Oncology, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas.
authors: Georgina N
authors: GN
authors: Armstrong
authors: Department of Pediatrics, Division of Hematology-Oncology, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas.
authors: Yanhong
authors: Y
authors: Liu
authors: Department of Pediatrics, Division of Hematology-Oncology, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas.
authors: Spyros
authors: S
authors: Tsavachidis
authors: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas.
authors: Shalini N
authors: SN
authors: Jhangiani
authors: Department of Pediatrics, Division of Hematology-Oncology, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas.
authors: Sharon E
authors: SE
authors: Plon
authors: Department of Pediatrics, Division of Hematology-Oncology, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas.
authors: Ching C
authors: CC
authors: Lau
authors: 1] Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut [2] Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts.
authors: Elizabeth B
authors: EB
authors: Claus
authors: Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio.
authors: Jill S
authors: JS
authors: Barnholtz-Sloan
authors: 1] Department of Epidemiology and Biostatistics, Georgia State University School of Public Health, Atlanta, Georgia [2] Cancer Control and Prevention Program, Department of Community and Family Medicine, Duke University Medical Center, Durham, North Carolina.
authors: Dora
authors: D
authors: Il'yasova
authors: Cancer Control and Prevention Program, Department of Community and Family Medicine, Duke University Medical Center, Durham, North Carolina.
authors: Joellen
authors: J
authors: Schildkraut
authors: Department of Surgery, Duke University Medical Center, Durham, North Carolina.
authors: Francis
authors: F
authors: Ali-Osman
authors: 1] Cancer and Radiation Epidemiology Unit, Gertner Institute, Chaim Sheba Medical Center, Tel Hashomer [2] Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors: Siegal
authors: S
authors: Sadetzki
authors: 1] Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark [2] Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors: Christoffer
authors: C
authors: Johansen
authors: Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, United Kingdom.
authors: Richard S
authors: RS
authors: Houlston
authors: Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Rochester, Minnesota.
authors: Robert B
authors: RB
authors: Jenkins
authors: Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Rochester, Minnesota.
authors: Daniel
authors: D
authors: Lachance
authors: Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: Sara H
authors: SH
authors: Olson
authors: Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors: Jonine L
authors: JL
authors: Bernstein
authors: Department of Neurology, NorthShore University HealthSystem, Evanston, Illinois.
authors: Ryan T
authors: RT
authors: Merrell
authors: Department of Neurological Surgery, University of California, San Francisco, San Francisco, California.
authors: Margaret R
authors: MR
authors: Wrensch
authors: Department of Public Health Services, University of Alberta, Edmonton, Alberta, Canada.
authors: Faith G
authors: FG
authors: Davis
authors: Departments of Neurology, Neurosurgery, and Preventive Medicine, The University of Southern California Keck School of Medicine, Los Angeles, California.
authors: Rose
authors: R
authors: Lai
authors: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Sanjay
authors: S
authors: Shete
authors: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Kenneth
authors: K
authors: Aldape
authors: Department of Community and Family Medicine, Department of Genetics, Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth; Hanover, New Hampshire.
authors: Christopher I
authors: CI
authors: Amos
authors: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas.
authors: Donna M
authors: DM
authors: Muzny
authors: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas.
authors: Richard A
authors: RA
authors: Gibbs
authors: Department of Radiation Sciences Oncology, Umeå University, Umeå, Sweden.
authors: Beatrice S
authors: BS
authors: Melin
authors: Department of Pediatrics, Division of Hematology-Oncology, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas.
authors: Melissa L
authors: ML
authors: Bondy
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002886:Chromosomes, Human, Pair 17; D005190:Family; D005260:Female; D008040:Genetic Linkage; D014644:Genetic Variation; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D017422:Sequence Analysis, DNA; D055815:Young Adult
references: Lung Cancer. 2013 Aug;81(2):266-72
references: 23711689
references: Proc Natl Acad Sci U S A. 2006 Apr 11;103(15):5929-34
references: 16585525
references: Cancer Res. 2011 Dec 15;71(24):7568-75
references: 22037877
references: Expert Opin Investig Drugs. 2009 Aug;18(8):1061-83
references: 19555299
references: Genome Biol. 2011;12(1):R6
references: 21247443
references: Nat Genet. 2014 Mar;46(3):310-5
references: 24487276
references: Nat Methods. 2010 Apr;7(4):248-9
references: 20354512
references: Fam Cancer. 2010 Sep;9(3):413-21
references: 20455025
references: Bioinformatics. 2009 Jul 15;25(14):1754-60
references: 19451168
references: J Cell Biol. 2006 Nov 6;175(3):383-8
references: 17074887
references: Hum Genet. 2012 Dec;131(12):1877-88
references: 22886559
references: Am J Dermatopathol. 2015 Jan;37(1):38-45
references: 25033008
references: Nature. 2012 Nov 1;491(7422):56-65
references: 23128226
references: Nat Rev Cancer. 2004 Mar;4(3):177-83
references: 14993899
references: PLoS Comput Biol. 2010 Dec 02;6(12):e1001025
references: 21152010
references: Cancer Res. 2002 Jul 1;62(13):3798-802
references: 12097292
references: J Clin Endocrinol Metab. 2009 Nov;94(11):4613-8
references: 19820019
references: BMC Bioinformatics. 2014 Jan 29;15:30
references: 24475911
references: Nat Genet. 2009 Aug;41(8):899-904
references: 19578367
references: Cancer Res. 1990 Apr 15;50(8):2322-9
references: 2156617
references: J Hepatol. 2011 Mar;54(3):529-37
references: 21109326
references: Eur J Cancer. 2013 Apr;49(6):1335-45
references: 23290425
references: Analyst. 2010 Jun;135(6):1315-9
references: 20498880
references: Tumour Biol. 2013 Oct;34(5):2849-55
references: 23696027
references: Virchows Arch. 2012 Sep;461(3):313-22
references: 22851038
references: Br J Cancer. 1999 Apr;79(11-12):1828-35
references: 10206300
references: Cell Cycle. 2006 Aug;5(16):1880-5
references: 16929179
references: Cancer Res. 1991 Aug 1;51(15):3972-81
references: 1713123
references: Nucleic Acids Res. 2010 Sep;38(16):e164
references: 20601685
references: PLoS One. 2013 Dec 09;8(12):e81348
references: 24349057
references: Nat Genet. 2011 May;43(5):491-8
references: 21478889
references: Nat Rev Cancer. 2012 Jul 24;12(8):527-39
references: 22825217
references: Neuro Oncol. 2014 Jul;16(7):896-913
references: 24842956
references: Curr Opin Neurol. 2013 Dec;26(6):688-92
references: 24184969
references: Cancer. 2009 Jun 15;115(12):2671-83
references: 19326449
references: Am J Epidemiol. 2010 Nov 15;172(10):1099-107
references: 20858744
references: Cancer Res. 1999 Nov 1;59(21):5403-7
references: 10554005
references: Nat Clin Pract Neurol. 2006 Sep;2(9):494-503; quiz 1 p following 516
references: 16932614
references: Genome Res. 2005 Jul;15(7):901-13
references: 15965027
references: Curr Opin Genet Dev. 2010 Jun;20(3):239-44
references: 20211558
references: Tumour Biol. 2014 Aug;35(8):7685-91
references: 24801907
references: J Exp Clin Cancer Res. 2013 Sep 19;32:69
references: 24330581
references: Cytoskeleton (Hoboken). 2013 May;70(5):281-95
references: 23568824
references: Cancer Epidemiol Biomarkers Prev. 2012 Dec;21(12):2242-51
references: 22962404
references: Mol Biol Cell. 2011 Sep;22(17):3070-80
references: 21737685
references: Bioinformatics. 2009 Aug 15;25(16):2078-9
references: 19505943
references: Asian Pac J Cancer Prev. 2013;14(12):7635-8
references: 24460345
references: Oncoimmunology. 2012 Oct 1;1(7):1194-1196
references: 23170277
references: Nature. 2013 Jan 10;493(7431):216-20
references: 23201682
references: Cancer Epidemiol Biomarkers Prev. 2007 Sep;16(9):1730-4
references: 17855690
references: Int J Cancer. 2013 May 15;132(10):2464-8
references: 23115063
references: Neuro Oncol. 2013 Nov;15 Suppl 2:ii1-56
references: 24137015
references: Gene. 2010 Oct 15;466(1-2):16-25
references: 20600703
references: Nat Protoc. 2009;4(7):1073-81
references: 19561590
references: Tumour Biol. 2014 Jul;35(7):6949-54
references: 24740566
references: Acta Neuropathol. 2005 Jan;109(1):93-108
references: 15685439