title: NLRP7 and the genetics of post-molar choriocarcinomas in Senegal.
abstract: Gestational choriocarcinomas are malignant tumors of trophoblastic cells that affect 5-25% of women with sporadic hydatidiform moles (HMs) depending on countries and studies. Nucleotide binding and oligomerization domain-like receptor protein 7 (NLRP7) is a major gene responsible for recurrent HMs and recently mutations in this gene have also been shown in 13% of women with sporadic, non-recurrent  moles. To investigate the role of NLRP7 in the genetic susceptibility for the malignant degeneration of moles, we sequenced its 11 exons in 43 Senegalese patients with post-molar choriocarcinomas. We report the presence of three novel NLRP7 variants that were found only in patients but not in 100 controls from the Senegalese general population, 100 controls from the Tunisian general population, and 100 controls from the Canadian population. In addition, this analysis revealed significant differences in the frequencies of four non-synonymous NLRP7 variants between European and Senegalese controls with the biggest difference being for variant G487E present at a minor allele frequency of 3.5% in Europeans, 18.1% in Tunisians and 45.6% in Senegalese. Comparing human NLRP7 and its paralog, NLRP2, with their mammalian counterparts revealed that allele E at position 487 is most likely the ancestral allele that was acquired in Africa but driven to low frequencies in Europeans and Asians due to migration, population bottlenecks and selective pressures. This study is the first attempt to investigate the role of NLRP7 in choriocarcinomas and highlights the higher frequencies of NLRP7 variants in the general Senegalese and Tunisian populations both known to have higher frequencies of moles and choriocarcinomas.
authors.affiliation: Department of Human Genetics, Montreal General Hospital Research Institute, McGill University Health Centre, L3-121 1650 Cedar Avenue, Montreal, Quebec, Canada P.Q. H3G 1A4. rima.slim@muhc.mcgill.ca
authors.forename: Rima
authors.initials: R
authors.lastname: Slim
authors.forename: Philippe
authors.initials: P
authors.lastname: Coullin
authors.forename: Ange-Lucien
authors.initials: AL
authors.lastname: Diatta
authors.forename: Wafaa
authors.initials: W
authors.lastname: Chebaro
authors.forename: David
authors.initials: D
authors.lastname: Courtin
authors.forename: Sonia
authors.initials: S
authors.lastname: Abdelhak
authors.forename: Andre
authors.initials: A
authors.lastname: Garcia
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000595:Amino Acid Sequence; D002822:Choriocarcinoma / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D006828:Hydatidiform Mole / Q000235:genetics* / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D011247:Pregnancy; D012675:Senegal; D016415:Sequence Alignment; D014594:Uterine Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C502448:NLRP7 protein, human