Whole exome sequencing identifies PLEC , EXO5 and DNAH7 as novel susceptibility genes in testicular cancer
| Autor: | Lucia Inglada Pérez, Francisco Zambrana, María José Juan Fita, Cristina López, S. Ros, Alicia Barroso, Ana María Autran, Isabel Lorenzo‐Lorenzo, Guillermo Pita, Ignacio Duran, Xavier Garcia del Muro, Fatima Al-Shahrour, Javier Benitez, Vanesa Quiroga, Enrique González Billalabeitia, Javier Sastre, Miguel Urioste, Héctor Tejero, Juan Moreno, Antonio Fernández Aramburo, Claudia Valverde, Juan Carlos Triviño, Patricia Iranzo, Beatriz Paumard-Hernández, Pablo Maroto, Oriol Calvete |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Exonucleases Male 0301 basic medicine Cancer Research Heredity Adolescent Testicular Germ Cell Tumor Susceptibility gene Disease Biology Logistic regression whole exome sequencing Young Adult 03 medical and health sciences 0302 clinical medicine Testicular Neoplasms Risk Factors Exome Sequencing medicine Humans Exome Genetic Predisposition to Disease Child Exome sequencing Testicular cancer Aged Genetics susceptibility risk variants Infant Axonemal Dyneins Middle Aged medicine.disease Pedigree 3. Good health 030104 developmental biology Oncology Case-Control Studies Child Preschool 030220 oncology & carcinogenesis testicular germ cell tumor Plectin Female Age of onset |
| Zdroj: | International Journal of Cancer |
| ISSN: | 1097-0215 0020-7136 |
| Popis: | Testicular germ cell tumors (TGCTs) are a clinically and pathologically heterogeneous disease, and little is known of its genetic basis. Only low susceptibility risk loci have been identified for both sporadic and familial cases. Therefore, we tried to identify new susceptibility genes responsible for familial testicular cancer that may contribute to increasing our knowledge about the genetic basis of the disease. Nineteen Spanish families with at least two affected individuals with TGCT were selected. WES was performed on those individuals using an Illumina Hiseq2000 sequencing platform. Data were analyzed under a monogenic and polygenic model of inheritance, and candidate variants were evaluated in a case-control association study performed on 391 Spanish sporadic cases and 1,170 healthy Spanish controls. Results were replicated in a second series consisting of 101 TGCTs from the Cancer Genome Atlas (TGCA) and 27,000 controls from the Exome Aggregation Consortium (ExAC) database. Logistic regression was carried out to analyze the association strength (risk) of candidate variants obtained among cases and controls in different populations. Despite the sample size, we detected a significant earlier age of onset in familial TGCT (28y) than sporadic cases (33y), using a Mann-Whitney U test. We identified significant variants in the comparative study of TGCT cases (391) versus controls (almost 1,170), and three of them [PLEC (OR = 6.28, p = 6.42 × 10-23 ) (p.Arg2016Trp), EXO5 (OR = 3.37, p = 4.82 × 10-09 ) (p.Arg344AlafsTer10) and DNAH7 (OR = 1.64, p = 0.048)] were replicated as potential candidates that may contribute to explaining the genetic basis of TGCT. |
| Databáze: | OpenAIRE |
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