The histone acetyltransferase hMOF is frequently downregulated in primary breast carcinoma and medulloblastoma and constitutes a biomarker for clinical outcome in medulloblastoma.
Loss of H4 lysine 16 (H4K16) acetylation was shown to be a common feature in human cancer. However, it remained unclear which enzyme is responsible for the loss of this modification. Having recently identified the histone acetyltransferase human MOF (hMOF) to be required for bulk H4K16 acetylation, here we examined the involvement of hMOF expression and H4K16 acetylation in breast cancer and medulloblastoma. Analysis of a recent mRNA expression profiling study in breast cancer (n = 100 cases) and an array-CGH screen in medulloblastomas (n = 102 cases), revealed downregulation in 40% and genomic loss in 11% of cases, respectively. We investigated hMOF protein expression as well as H4K16 acetylation in large series of primary breast carcinomas (n = 298) and primary medulloblastomas (n = 180) by immunohistochemistry. In contrast to nontransformed control tissues, significant fractions of both primary breast carcinomas and medulloblastomas showed markedly reduced hMOF mRNA and protein expression. In addition, hMOF protein expression tightly correlated with acetylation of H4K16 in all tested samples. For medulloblastoma, downregulation of hMOF protein expression was associated with lower survival rates identifying hMOF as an independent prognostic marker for clinical outcome in univariate as well as multivariate analyses.
Department of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Stefan
S
Pfister
Stephen
S
Rea
Mikko
M
Taipale
Frank
F
Mendrzyk
Beate
B
Straub
Carina
C
Ittrich
Olaf
O
Thuerigen
Hans Peter
HP
Sinn
Asifa
A
Akhtar
Peter
P
Lichter
D000107:Acetylation; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000201:enzymology*; D001943:Breast Neoplasms / Q000201:enzymology*; D004273:DNA, Neoplasm / Q000235:genetics; D015536:Down-Regulation; D020869:Gene Expression Profiling; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006801:Humans; D008527:Medulloblastoma / Q000201:enzymology*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D012333:RNA, Messenger; D051548:Histone Acetyltransferases; C496552:KAT8 protein, human