The
death-associated protein kinase (
DAP kinase) was initially identified as a positive mediator of programmed cell death induced by
interferon-gamma. To investigate the potential role and the alteration of the
DAP kinase gene in soft tissue
leiomyosarcoma (LMS), we first searched for homozygous deletion and promoter hypermethylation in 45 LMSs for which genomic
DNA was available, using differential PCR and methylation-specific PCR, respectively. Promoter methylation was recognized in 10 of 45 cases (22%), and homozygous deletion was detected in 3 of 45 cases (7%). p53 mutation was detected in 11 of 45 LMS cases (24%). Cases with
DAP kinase alteration or p53 mutation showed a close correlation with high French Federation of
Cancer Centers grade or with poor prognosis (P = 0.0244, P = 0.0491, respectively). Next, to determine that
DAP kinase promoter methylation or homozygous deletion is involved in the down-regulation of
DAP kinase expression, we examined the expression of
DAP kinase protein by immunohistochemistry. Decreased expression of
DAP kinase protein was recognized in 13 of 45 LMS cases (29%). Seven of 13 cases (54%) with decreased expression of
DAP kinase protein revealed promoter methylation or homozygous deletion of
DAP kinase, and the methylation status or homozygous deletion of its gene showed a close correlation with decreased
DAP kinase expression (P = 0.0300). In conclusion, although
DAP kinase alteration was relatively rare,
DAP kinase alteration and/or p53 mutation may associate with
tumor progression in soft-tissue LMSs. Furthermore, although further detailed analyses are necessary, promoter methylation or homozygous deletion status of
DAP kinase may present a major alternative mechanism of a loss of or decrease in
DAP kinase expression.