Whole-genome sequencing identifies STAT4 as a putative susceptibility gene in classic Kaposi sarcoma

Mervi Aavikko, Eevi Kaasinen, Janne K. Nieminen, Minji Byun, Iikki Donner, Roberta Mancuso, Pasquale Ferrante, Mario Clerici, Lucia Brambilla, Athanasia Tourlaki, Ronit Sarid, Emma Guttman-Yassky, Minna Taipale, Ekaterina Morgunova, Pirita Pekkonen, Päivi M. Ojala, Eero Pukkala, Jean Laurent Casanova, Outi Vaarala, Pia VahteristoLauri A. Aaltonen

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


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.

Original languageEnglish
Pages (from-to)1842-1851
Number of pages10
JournalJournal of Infectious Diseases
Issue number11
StatePublished - 1 Jun 2015


  • HHV8
  • STAT4
  • classic Kaposi sarcoma
  • genetic predisposition
  • genome sequencing


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