Whole-Genome Sequencing Identifies STAT4 as a Putative Susceptibility Gene in Classic Kaposi Sarcoma.
J Infect Dis
; 211(11): 1842-51, 2015 Jun 01.
Article
en En
| MEDLINE
| ID: mdl-25492914
ABSTRACT
BACKGROUND:
Classic Kaposi sarcoma (cKS) is an inflammatory tumor caused by human herpesvirus 8 (HHV-8) commonly observed in elderly men of Mediterranean origin. We studied a Finnish family of 5 affected individuals in 2 generations. Except for atypical mycobacterial infection of the index case, the affected individuals did not have notable histories of infection.METHODS:
We performed genome and exome sequencing and mapped shared chromosomal regions to identify genetic predisposition in the family.RESULTS:
We identified 12 protein-coding candidate variants that segregated in the 3 affected cousins from whom we had samples. The affected mother of the index case was an obligatory carrier. Among the 12 candidates was a rare heterozygous substitution rs141331848 (c.1337C>T, p.Thr446Ile) in the DNA-binding domain of STAT4. The variant was not present in 242 Finnish control genomes or 180 additional regional controls. Activated T-helper cells from the HHV-8-negative variant carriers showed reduced interferon γ production, compared with age and sex matched wild-type individuals. We screened STAT4 in additional 18 familial KS cases and the variant site from 56 sporadic KS cases but detected no pathogenic mutations.CONCLUSIONS:
Our data suggest that STAT4 is a potential cKS-predisposition gene, but further functional and genetic validation is needed.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Sarcoma de Kaposi
/
Predisposición Genética a la Enfermedad
/
Factor de Transcripción STAT4
Tipo de estudio:
Prognostic_studies
Límite:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
J Infect Dis
Año:
2015
Tipo del documento:
Article