Frequent abnormalities of TSG101 transcripts in human prostate cancer

Abstract

TSG101 has been identi®ed as a candidate tumor suppressor gene and abnormal transcripts have been identi®ed in a substantial fraction of breast cancers. To determine whether TSG101 expression is commonly altered in other tumors, a series of 15 primary and metastatic prostate cancers were analysed by reverse transcriptase-PCR ampli®cation. Abnormal transcripts with extensive deletions in the coding region were found in nine of these tumors, while only the normal transcript was found in control and benign prostatic hypertrophy tissues. More than one abnormal transcript was found in four of these nine cases and distinct abnormal TSG101 transcripts were found in separate biopsies taken from one tumor. Importantly, the normal TSG101 transcript was undetectable in two metastatic prostate cancers, indicating the absence of TSG101 protein. Sequence analysis demonstrated that there were at least six distinct deletions, with four of these deletions found in more than one tumor sample. The most commonly identi®ed deletion, from bp 153 to 1055, was identical to a deletion reported previously in breast cancer. These results demonstrate that TSG101 transcripts are frequently abnormal in prostate cancer and suggest that loss of TSG101 protein contributes to disease development or progression.

Expression of a new isoform of the tumor susceptibility TSG101 protein lacking a leucine zipper domain in Burkitt lymphoma cell lines

“…Most of the TSG101 deletions detected in BL and resulting in non coding transcripts are similar to those reported in breast (Lee and Feinberg, 1997;Li et al, 1997;Steiner et al, 1997), prostate carcinomas (Sun et al, 1997), small cell lung carcinoma (Oh et al, 1998) and acute myeloid leukemia (Lin et al, 1998). These splicing aberrations can also be detected in normal cells although at a much lower frequency, suggesting there is a biological selection for them in tumor cells (Gayther et al, 1997;Oh et al, 1998).…”

“…These splicing aberrations can also be detected in normal cells although at a much lower frequency, suggesting there is a biological selection for them in tumor cells (Gayther et al, 1997;Oh et al, 1998). Among these, the joining of nucleotides 153 ± 1055 represents the most common and abundant aberrant transcript in all types of tumors breast (Lee and Feinberg, 1997;Li et al, 1997;Lin et al, 1998;Oh et al, 1998;Steiner et al, 1997;Sun et al, 1997). In this report we have identi®ed a splicing variant that can code for a truncated form of the TSG101 protein, lacking a leucine zipper dimerization domain, that can have biological implications and its presence is detected in 16 of 22 or 72% of the BL cell lines.…”

“…All cell lines show as RT-PCR products, in addition to a normal size band of 1146 nucleotides, several additional smaller bands (Figure 2) that are likely to be derived from aberrant transcripts. One of the shorter bands is common to all cell lines and represent an aberrant transcript resulting from splicing of nucleotides 154 ± 1054 (Lee and Feinberg, 1997;Li et al, 1997;Sun et al, 1997). Because of the high number of di erent shorter bands, rather than to clone all of them from the di erent cell lines, we decided to clone a wide range of bands from two cell lines, J1 and Namalwa, to cover a wide range of sizes below the normal one and characterize them by nucleotide sequence.…”

“…Total RNA from di erent cell lines was converted into cDNA and subject to a nested PCR as previously reported. The short and intense band of 300 nucleotides represents the most common non-coding aberrant message previously reported in other tumors (Lee and Feinberg, 1997;Li et al, 1997;Sun et al, 1997). jX174 DNA digested with HaeIII was used as size marker within exon 1.…”

“…Aberrantly spliced TSG101 messages with loss of coding exons are frequently detected in breast (Lee and Feinberg, 1997;Steiner et al, 1997), prostate (Sun et al, 1997), small cell lung carcinomas (Oh et al, 1998) and acute myeloid leukemia (Lin et al, 1998). In some cases the aberrant messages might be the result of rearrangements at the DNA level (Lee and Feinberg, 1997;Steiner et al, 1997).…”