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Genome-wide linkage screen for testicular germ cell tumour susceptibility loci.

Gillian Crockford 1 Rachel Linger 2 Sarah Hockley 2 Darshna Dudakia 2 Lola Johnson 2 Robert Huddart 3 Kathy Tucker 4 Michael Friedlander 4 Kelly-Anne Phillips 5 David Hogg 6 Michael Jewett 6 Radka Lohynska 7 Gedske Daugaard 8 Stéphane Richard 9, 10 Agnès Chompret 11 Catherine Bonaïti-Pellié 12 Axel Heidenreich 13 Peter Albers 14 Edith Olah 15 Lajos Geczi 15 Istvan Bodrogi 15 Wilma Ormiston 16 Peter Daly 16 Parry Guilford 17 Sophie Fosså 18 Ketil Heimdal 18 Sergei Tjulandin 19 Ludmila Liubchenko 19 Hans Stoll 20 Walter Weber 20 David Forman 21 Timothy Oliver 22 Lawrence Einhorn 22 Mary Mcmaster 23 Joan Kramer 23 Mark Greene 23 Barbara Weber 24 Katherine Nathanson 24 Victoria Cortessis 25 Douglas Easton 26 D Timothy Bishop 1 Michael Stratton 2 Elizabeth Rapley 2, *
* Corresponding author
1 Genetic Epidemiology Division, Cancer Research UK Clinical Centre
2 Section of Cancer Genetics
3 Academic Radiotherapy Unit
4 Dept of Medical Oncology, Division of Medicine
5 Dept of Haematology and Medical Oncology
6 Princess Margaret Hospital
7 Dept of Radiotherapy and Oncology
8 Dept of Oncology
9 GO - UMR 8125 - Génétique oncologique
10 Service d'urologie
11 Onco-génétique
Département de médecine oncologique [Gustave Roussy]
12 Inserm U535 - Génétique épidémiologique et structures des populations humaines
13 Dept of Urological Oncology
14 Department of Urology
15 Department of Molecular Genetics and Department of Chemotherapy
16 Department of Medical Oncology
17 Cancer Genetics Laboratory
18 Departments of Clinical Cancer Research and genetics
19 Laboratory of Clinical Genetics
20 Medical Oncology
21 Cancer Epidemiology
22 Department of Medical Oncology
23 Clinical Genetics Branch, Division of Cancer Epidemiology & Genetics
24 Depts of Medicine and Biostatistics and Epidemology
25 Department of Preventive Medicine
26 Cancer Research U.K. Genetic Epidemiology Unit
Abstract : A family history of disease is a strong risk factor for testicular germ cell tumour (TGCT). In order to identify the location of putative TGCT susceptibility gene(s) we conducted a linkage search in 237 pedigrees with two or more cases of TGCT. One hundred and seventy-nine pedigrees were evaluated genome-wide with an average inter-marker distance of 10 cM. An additional 58 pedigrees were used to more intensively investigate several genomic regions of interest. Genetic linkage analysis was performed with the ALLEGRO software using two model-based parametric analyses and a non-parametric analysis. Six genomic regions on chromosomes 2p23, 3p12, 3q26, 12p13-q21, 18q21-q23 and Xq27 showed heterogeneity LOD (HLOD) scores of greater than 1, with a maximum HLOD of 1.94 at 3q26. Genome-wide simulation studies indicate that the observed number of HLOD peaks greater than one does not differ significantly from that expected by chance. A TGCT locus at Xq27 has been previously reported. Of the 237 pedigrees examined in this study, 66 were previously unstudied at Xq27, no evidence for linkage to this region was observed in this new pedigree set. Overall, the results indicate that no single major locus can account for the majority of the familial aggregation of TGCT, and suggests that multiple susceptibility loci with weak effects contribute to the disease.
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https://www.hal.inserm.fr/inserm-00127763
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Gillian Crockford, Rachel Linger, Sarah Hockley, Darshna Dudakia, Lola Johnson, et al.. Genome-wide linkage screen for testicular germ cell tumour susceptibility loci.. Human Molecular Genetics, Oxford University Press (OUP), 2006, 15 (3), pp.443-51. ⟨10.1093/hmg/ddi459⟩. ⟨inserm-00127763⟩

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