RT Journal Article
T1 Whole exome sequencing identifies PLEC, EXO5 and DNAH7 as novel susceptibility genes in testicular cancer.
A1 Paumard-Hernández, Beatriz
A1 Calvete, Oriol
A1 Inglada Pérez, Lucia
A1 Tejero, Héctor
A1 Al-Shahrour, Fátima
A1 Pita, Guillermo
A1 Barroso, Alicia
A1 Carlos Triviño, Juan
A1 Urioste, Miguel
A1 Valverde, Claudia
A1 González Billalabeitia, Enrique
A1 Quiroga, Vanesa
A1 Francisco Rodríguez Moreno, Juan
A1 Fernández Aramburo, Antonio
A1 López, Cristina
A1 Maroto, Pablo
A1 Sastre, Javier
A1 José Juan Fita, María
A1 Duran, Ignacio
A1 Lorenzo-Lorenzo, Isabel
A1 Iranzo, Patricia
A1 García Del Muro, Xavier
A1 Ros, Silverio
A1 Zambrana, Francisco
A1 María Autran, Ana
A1 Benítez, Javier
K1 susceptibility risk variants
K1 testicular germ cell tumor
K1 whole exome sequencing
AB 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.
YR 2018
FD 2018-08-09
LK http://hdl.handle.net/10668/12468
UL http://hdl.handle.net/10668/12468
LA en
DS RISalud
RD Apr 6, 2025