Prevalence of chromosomal rearrangements involving non-ETS genes in prostate cancer

Abstract

Prostate cancer is characterized by structural rearrangements, most frequently including translocations between androgen-dependent genes and members of the ETS family of transcription factor like TMPRSS2:ERG. In a recent whole genome sequencing study we identified 140 gene fusions that were unrelated to ETS genes in 11 prostate cancers. The aim of the present study was to estimate the prevalence of non-ETS gene fusions. We randomly selected 27 of these rearrangements and analyzed them by fluorescence in situ hybridization (FISH) in a tissue microarray format containing 500 prostate cancers. Using break-apart FISH probes for one fusion partner each, we found rearrangements of 13 (48%) of the 27 analyzed genes in 300-400 analyzable cancers per gene. Recurrent breakage, often accompanied by partial deletion of the genes, was found for NCKAP5, SH3BGR and TTC3 in 3 (0.8%) tumors each, as well as for ARNTL2 and ENOX1 in 2 (0.5%) cancers each. One rearranged tumor sample was observed for each of VCL, ZNF578, IMMP2L, SLC16A12, PANK1, GPHN, LRP1 and ZHX2. Balanced rearrangements, indicating possible gene fusion, were found for ZNF578, SH3BGR, LPR12 and ZHX2 in individual cancers only. The results of the present study confirm that rearrangements involving non-ETS genes occur in prostate cancer, but demonstrate that they are highly individual and typically non-recurrent.

Appraising the relevance of DNA copy number loss and gain in prostate cancer using whole genome DNA sequence data

“…THSD7B , a gene involved in the TGFβ signaling pathway, has been previously found to be the target for mutations [ 45 ]. NCKAP5 is a gene in the large region of inversion at 2q21.3-q22.1 and has been observed to be rearranged in prostate cancer by FISH [ 46 ]. Regions of inversions were also observed in GISTIC detected deletions ( S15 Table ).…”

HBV suppresses ZHX2 expression to promote proliferation of HCC through miR‐155 activation

“…20 Another study found reduced nuclear ZHX2 protein levels in HCC compared with surrounding non-tumor tissue, demonstrating that ZHX2 might also be regulated posttranscriptionally. [22][23][24] Chromosomal rearrangement at t(4;8)(q27;q24) that include the ZHX2 gene are associated with decreased ZHX2 expression in Hodgkin lymphoma. 21 Polymorphisms in the ZHX2 gene and disregulated ZHX2 expression have been reported in other cancers, including multiple myeloma, thyroid carcinoma and prostate cancer.…”

“…21 Polymorphisms in the ZHX2 gene and disregulated ZHX2 expression have been reported in other cancers, including multiple myeloma, thyroid carcinoma and prostate cancer. [22][23][24] Chromosomal rearrangement at t(4;8)(q27;q24) that include the ZHX2 gene are associated with decreased ZHX2 expression in Hodgkin lymphoma. 25 Since HBV is one of the common risk factors for HCC, we hypothesized that HBV might also influence ZHX2 expression.…”

Analysis of head and neck carcinoma progression reveals novel and relevant stage-specific changes associated with immortalisation and malignancy

“…Some genes such as PTPRD, LRP1B and LINGO2 , which are target for homozygous deletions in HNSCC cell lines, showed frequent hemizygous deletions in the PPOL cell lines suggesting further selection in progression to HNSCC. Deletion of NCKAP5 was explored a little further (S7) as rare SCNAs involving NCKAP5 have been reported recently in HNSCC (3) (in supplementary data) and in prostate cancer (27). Potentially deleterious mutations have been reported in COSMIC (S7 Table).…”