caa a22 4500 445331321 CHVBK 20180317142738.0 cr unu---uuuuu 170323e20110601xx s 000 0 eng 10.1007/s10689-010-9408-8 doi (NATIONALLICENCE)springer-10.1007/s10689-010-9408-8 Linkage to chromosome 2q32.2-q33.3 in familial serrated neoplasia (Jass syndrome) [Elektronische Daten] [Aedan Roberts, Derek Nancarrow, Mark Clendenning, Daniel Buchanan, Mark Jenkins, David Duggan, Darin Taverna, Diane McKeone, Rhiannon Walters, Michael Walsh, Bruce Young, Jeremy Jass, Christophe Rosty, Michael Gattas, Elise Pelzer, John Hopper, Jack Goldblatt, Jill George, Graeme Suthers, Kerry Phillips, Susan Parry, Sonja Woodall, Julie Arnold, Kathy Tucker, Amanda Muir, Musa Drini, Finlay Macrae, Polly Newcomb, John Potter, Erika Pavluk, Annika Lindblom, Joanne Young] Causative genetic variants have to date been identified for only a small proportion of familial colorectal cancer (CRC). While conditions such as Familial Adenomatous Polyposis and Lynch syndrome have well defined genetic causes, the search for variants underlying the remainder of familial CRC is plagued by genetic heterogeneity. The recent identification of families with a heritable predisposition to malignancies arising through the serrated pathway (familial serrated neoplasia or Jass syndrome) provides an opportunity to study a subset of familial CRC in which heterogeneity may be greatly reduced. A genome-wide linkage screen was performed on a large family displaying a dominantly-inherited predisposition to serrated neoplasia genotyped using the Affymetrix GeneChip Human Mapping 10K SNP Array. Parametric and nonparametric analyses were performed and resulting regions of interest, as well as previously reported CRC susceptibility loci at 3q22, 7q31 and 9q22, were followed up by finemapping in 10 serrated neoplasia families. Genome-wide linkage analysis revealed regions of interest at 2p25.2-p25.1, 2q24.3-q37.1 and 8p21.2-q12.1. Finemapping linkage and haplotype analyses identified 2q32.2-q33.3 as the region most likely to harbour linkage, with heterogeneity logarithm of the odds (HLOD) 2.09 and nonparametric linkage (NPL) score 2.36 (P=0.004). Five primary candidate genes (CFLAR, CASP10, CASP8, FZD7 and BMPR2) were sequenced and no segregating variants identified. There was no evidence of linkage to previously reported loci on chromosomes 3, 7 and 9. The Author(s), 2010 Serrated neoplasia nationallicence Familial cancer nationallicence Linkage nationallicence CRC : Colorectal cancer nationallicence HLOD : Heterogeneity logarithm of the odds nationallicence LOD : Logarithm of the odds nationallicence MMR : Mismatch repair nationallicence MSI : Microsatellite instability nationallicence MSI-V : Microsatellite instability-variable nationallicence NPL : Nonparametric linkage nationallicence Roberts Aedan Familial Cancer Laboratory, Queensland Institute of Medical Research, 4006, Herston, QLD, Australia aut Nancarrow Derek Oncogenomics Laboratory, Queensland Institute of Medical Research, 4006, Herston, QLD, Australia aut Clendenning Mark Familial Cancer Laboratory, Queensland Institute of Medical Research, 4006, Herston, QLD, Australia aut Buchanan Daniel Familial Cancer Laboratory, Queensland Institute of Medical Research, 4006, Herston, QLD, Australia aut Jenkins Mark Centre for MEGA, School of Population Health, University of Melbourne, 3053, Carlton, VIC, Australia aut Duggan David Translational Genomics, Phoenix, AZ, USA aut Taverna Darin Translational Genomics, Phoenix, AZ, USA aut McKeone Diane Familial Cancer Laboratory, Queensland Institute of Medical Research, 4006, Herston, QLD, Australia aut Walters Rhiannon Familial Cancer Laboratory, Queensland Institute of Medical Research, 4006, Herston, QLD, Australia aut Walsh Michael Familial Cancer Laboratory, Queensland Institute of Medical Research, 4006, Herston, QLD, Australia aut Young Bruce Information Services, Queensland University of Technology, Kelvin Grove, QLD, Australia aut Jass Jeremy Department of Cellular Pathology, St Mark's Hospital, HA1 3UJ, Harrow, UK aut Rosty Christophe Familial Cancer Laboratory, Queensland Institute of Medical Research, 4006, Herston, QLD, Australia aut Gattas Michael Queensland Clinical Genetics Service, Royal Children's Hospital, 4029, Herston, QLD, Australia aut Pelzer Elise Queensland Clinical Genetics Service, Royal Children's Hospital, 4029, Herston, QLD, Australia aut Hopper John Centre for MEGA, School of Population Health, University of Melbourne, 3053, Carlton, VIC, Australia aut Goldblatt Jack Genetic Services of Western Australia, 6008, Subiaco, WA, Australia aut George Jill Genetic Services of Western Australia, 6008, Subiaco, WA, Australia aut Suthers Graeme South Australian Clinical Genetics Service, 5009, North Adelaide, SA, Australia aut Phillips Kerry South Australian Clinical Genetics Service, 5009, North Adelaide, SA, Australia aut Parry Susan Department of Gastroenterology, Middlemore Hospital, Auckland, New Zealand aut Woodall Sonja Familial Gastrointestinal Cancer Registry, Auckland City Hospital, Auckland, New Zealand aut Arnold Julie Familial Gastrointestinal Cancer Registry, Auckland City Hospital, Auckland, New Zealand aut Tucker Kathy Hereditary Cancer Clinic, Prince of Wales Hospital, 2031, Randwick, NSW, Australia aut Muir Amanda Department of Clinical Genetics, Royal North Shore Hospital, 2145, Sydney, NSW, Australia aut Drini Musa Department of Colorectal Medicine and Genetics, The Royal Melbourne Hospital, 3050, Parkville, VIC, Australia aut Macrae Finlay Department of Colorectal Medicine and Genetics, The Royal Melbourne Hospital, 3050, Parkville, VIC, Australia aut Newcomb Polly Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA aut Potter John Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA aut Pavluk Erika Familial Cancer Laboratory, Queensland Institute of Medical Research, 4006, Herston, QLD, Australia aut Lindblom Annika Department of Molecular Medicine, Karolinska Institute, Stockholm, Sweden aut Young Joanne Familial Cancer Laboratory, Queensland Institute of Medical Research, 4006, Herston, QLD, Australia aut Familial Cancer Springer Netherlands 10/2(2011-06-01), 245-254 1389-9600 10:2<245 2011 10 10689 https://doi.org/10.1007/s10689-010-9408-8 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10689-010-9408-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Roberts Aedan Familial Cancer Laboratory, Queensland Institute of Medical Research, 4006, Herston, QLD, Australia aut NATIONALLICENCE 700 1- Nancarrow Derek Oncogenomics Laboratory, Queensland Institute of Medical Research, 4006, Herston, QLD, Australia aut NATIONALLICENCE 700 1- Clendenning Mark Familial Cancer Laboratory, Queensland Institute of Medical Research, 4006, Herston, QLD, Australia aut NATIONALLICENCE 700 1- Buchanan Daniel Familial Cancer Laboratory, Queensland Institute of Medical Research, 4006, Herston, QLD, Australia aut NATIONALLICENCE 700 1- Jenkins Mark Centre for MEGA, School of Population Health, University of Melbourne, 3053, Carlton, VIC, Australia aut NATIONALLICENCE 700 1- Duggan David Translational Genomics, Phoenix, AZ, USA aut NATIONALLICENCE 700 1- Taverna Darin Translational Genomics, Phoenix, AZ, USA aut NATIONALLICENCE 700 1- McKeone Diane Familial Cancer Laboratory, Queensland Institute of Medical Research, 4006, Herston, QLD, Australia aut NATIONALLICENCE 700 1- Walters Rhiannon Familial Cancer Laboratory, Queensland Institute of Medical Research, 4006, Herston, QLD, Australia aut NATIONALLICENCE 700 1- Walsh Michael Familial Cancer Laboratory, Queensland Institute of Medical Research, 4006, Herston, QLD, Australia aut NATIONALLICENCE 700 1- Young Bruce Information Services, Queensland University of Technology, Kelvin Grove, QLD, Australia aut NATIONALLICENCE 700 1- Jass Jeremy Department of Cellular Pathology, St Mark's Hospital, HA1 3UJ, Harrow, UK aut NATIONALLICENCE 700 1- Rosty Christophe Familial Cancer Laboratory, Queensland Institute of Medical Research, 4006, Herston, QLD, Australia aut NATIONALLICENCE 700 1- Gattas Michael Queensland Clinical Genetics Service, Royal Children's Hospital, 4029, Herston, QLD, Australia aut NATIONALLICENCE 700 1- Pelzer Elise Queensland Clinical Genetics Service, Royal Children's Hospital, 4029, Herston, QLD, Australia aut NATIONALLICENCE 700 1- Hopper John Centre for MEGA, School of Population Health, University of Melbourne, 3053, Carlton, VIC, Australia aut NATIONALLICENCE 700 1- Goldblatt Jack Genetic Services of Western Australia, 6008, Subiaco, WA, Australia aut NATIONALLICENCE 700 1- George Jill Genetic Services of Western Australia, 6008, Subiaco, WA, Australia aut NATIONALLICENCE 700 1- Suthers Graeme South Australian Clinical Genetics Service, 5009, North Adelaide, SA, Australia aut NATIONALLICENCE 700 1- Phillips Kerry South Australian Clinical Genetics Service, 5009, North Adelaide, SA, Australia aut NATIONALLICENCE 700 1- Parry Susan Department of Gastroenterology, Middlemore Hospital, Auckland, New Zealand aut NATIONALLICENCE 700 1- Woodall Sonja Familial Gastrointestinal Cancer Registry, Auckland City Hospital, Auckland, New Zealand aut NATIONALLICENCE 700 1- Arnold Julie Familial Gastrointestinal Cancer Registry, Auckland City Hospital, Auckland, New Zealand aut NATIONALLICENCE 700 1- Tucker Kathy Hereditary Cancer Clinic, Prince of Wales Hospital, 2031, Randwick, NSW, Australia aut NATIONALLICENCE 700 1- Muir Amanda Department of Clinical Genetics, Royal North Shore Hospital, 2145, Sydney, NSW, Australia aut NATIONALLICENCE 700 1- Drini Musa Department of Colorectal Medicine and Genetics, The Royal Melbourne Hospital, 3050, Parkville, VIC, Australia aut NATIONALLICENCE 700 1- Macrae Finlay Department of Colorectal Medicine and Genetics, The Royal Melbourne Hospital, 3050, Parkville, VIC, Australia aut NATIONALLICENCE 700 1- Newcomb Polly Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA aut NATIONALLICENCE 700 1- Potter John Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA aut NATIONALLICENCE 700 1- Pavluk Erika Familial Cancer Laboratory, Queensland Institute of Medical Research, 4006, Herston, QLD, Australia aut NATIONALLICENCE 700 1- Lindblom Annika Department of Molecular Medicine, Karolinska Institute, Stockholm, Sweden aut NATIONALLICENCE 700 1- Young Joanne Familial Cancer Laboratory, Queensland Institute of Medical Research, 4006, Herston, QLD, Australia aut NATIONALLICENCE 773 0- Familial Cancer Springer Netherlands 10/2(2011-06-01), 245-254 1389-9600 10:2<245 2011 10 10689 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer