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The first large genomic study of prostate cancer in Chinese men found the signature fusion that dominates Western series is uncommon, and a different deletion takes its place.
Whole-genome and transcriptome sequencing was performed on tumour and matched benign tissue from 65 treatment-naive Chinese prostate cancer patients, with targeted deep sequencing of 293 prostate cancer-relevant genes in a further 145 tumours. A high frequency of CHD1 deletion was associated with a low rate of TMPRSS2-ERG fusion and a relatively high proportion of mutations in genes upstream of the androgen receptor. Five putative clustered deleted tumour suppressor genes were identified, with experimental and clinical evidence that PCDH9, deleted or lost in about 23% of tumours, functions as a tumour suppressor with prognostic value. Axon guidance pathway genes were frequently deregulated, including gain or amplification of PLXNA1 in about 17% of tumours, and increased PLXNA1 expression promoted tumour growth and independently predicted biochemical recurrence, metastasis and poor survival in multi-institutional cohorts.
It is the reason a prostate cancer fusion frequency quoted without an ancestry is unsafe. In this cohort the founder event that defines almost half of Western tumours is uncommon, and the fusion-negative, CHD1-deleted route dominates instead.
Shares TMPRSS2, TMPRSS2-ERG fusion (and the other ETS rearrangements), ERG, Prostate cancer (KEGG map).
Shares TMPRSS2, TMPRSS2-ERG fusion (and the other ETS rearrangements), ERG, Prostate cancer (KEGG map).
Shares Copy number alteration (CNA), Prostate cancer (KEGG map), Chromosomal instability & aneuploidy, Androgen receptor signalling.
Shares TMPRSS2, Copy number alteration (CNA), ERG, Prostate cancer (KEGG map).
Shares ERG, Prostate cancer (KEGG map), Androgen receptor signalling, Gene fusion.
Shares TMPRSS2-ERG fusion (and the other ETS rearrangements), Prostate cancer (KEGG map), Androgen receptor signalling, Gene fusion.
Shares TMPRSS2, TMPRSS2-ERG fusion (and the other ETS rearrangements), ERG, Prostate cancer (KEGG map).
Shares Copy number alteration (CNA), Chromosomal instability & aneuploidy, Androgen receptor signalling, Androgen receptor.