PT  - JOURNAL ARTICLE
AU  - Patrick R Benusiglio
AU  - Sophie Couvé
AU  - Brigitte Gilbert-Dussardier
AU  - Sophie Deveaux
AU  - Hélène Le Jeune
AU  - Mélanie Da Costa
AU  - Gaëlle Fromont
AU  - Françoise Memeteau
AU  - Mokrane Yacoub
AU  - Isabelle Coupier
AU  - Dominique Leroux
AU  - Arnaud Méjean
AU  - Bernard Escudier
AU  - Sophie Giraud
AU  - Anne-Paule Gimenez-Roqueplo
AU  - Christophe Blondel
AU  - Eric Frouin
AU  - Bin T Teh
AU  - Sophie Ferlicot
AU  - Brigitte Bressac-de Paillerets
AU  - Stéphane Richard
AU  - Sophie Gad
TI  - A germline mutation in <em>PBRM1</em> predisposes to renal cell carcinoma
AID  - 10.1136/jmedgenet-2014-102912
DP  - 2015 Jun 01
TA  - Journal of Medical Genetics
PG  - 426--430
VI  - 52
IP  - 6
4099  - http://jmg.bmj.com/content/52/6/426.short
4100  - http://jmg.bmj.com/content/52/6/426.full
SO  - J Med Genet2015 Jun 01; 52
AB  - Background Many cases of familial renal cell carcinoma (RCC) remain unexplained by mutations in the known predisposing genes or shared environmental factors. There are therefore additional, still unidentified genes involved in familial RCC. PBRM1 is a tumour suppressor gene and somatic mutations are found in 30–45% of sporadic clear cell (cc) RCC. Methods We selected 35 unrelated patients with unexplained personal history of ccRCC and at least one affected first-degree relative, and sequenced the PBRM1 gene. Results A germline frameshift mutation (c.3998_4005del [p.Asp1333Glyfs]) was found in one patient. The patient's mother, his sister and one niece also had ccRCC. The mutation co-segregated with the disease as the three affected relatives were carriers, while an unaffected sister was not, according with autosomal-dominant transmission. Somatic studies supported these findings, as we observed both loss of heterozygosity for the mutation and loss of protein expression in renal tumours. Conclusions We show for the first time that an inherited mutation in PBRM1 predisposes to RCC. International studies are necessary to estimate the contribution of PBRM1 to RCC susceptibility, estimate penetrance and then integrate the gene into routine clinical practice.