The XAGE family of cancer/testis‐associated genes: Alignment and expression profile in normal tissues, melanoma lesions and Ewing's sarcoma

Abstract

The existence of XAGE genes was first reported after database homology searches for PAGE-like sequences identified 3 XAGE EST clusters. One of these clusters, XAGE-1, has in later studies been identified as a cancer/testis-associated gene. Here, we report the expression profiles of all 3 reported XAGE genes, as well as several splice variants of XAGE-1, in normal human tissues, Ewing's sarcoma and melanocytic tumors. We also provide the genetic structure of the corresponding genes. Moreover, by searching the databases for XAGE homologues, we identified 3 additional GAGE-like genes. RT-PCR studies showed frequent expression in melanoma metastases and Ewing's sarcoma for 2 XAGE-1-derived transcripts. XAGE-2 was expressed at lower frequency in these tissues, while XAGE-3 was seen only in normal placenta. Due to a frameshift, the largest XAGE-1 putative protein is far less homologous to GAGE-like proteins than the other XAGEs. Interestingly, all GAGE-like genes contain a large secondary open reading frame, coding for putative proteins homologues to the XAGE-1 primary protein. The XAGE family of cancer/testis-associated genes is located on chromosome Xp11.21-Xp11.22. The data outline a superfamily of GAGE-like cancer/testis antigens, consisting of at least 19 genes.

XAGE‐1 mRNA Expression in Prostate Cancer and Antibody Response in Patients

“…Recent analysis using a cancer-profiling array showed that XAGE-1 mRNA was expressed in various types of cancer such as breast, lung and prostate cancer (7). XAGE-1b mRNA was expressed most frequently among the 4 transcript variants in metastatic melanoma (23). Using surgically-resected tumor specimens, we observed that XAGE-1b mRNA was expressed at high frequency in liver cancer (11/19, 58%) and lung adenocarcinoma (14/31, 45%), and low frequency in breast cancer (1/20, 5%).…”

“…It was reported that XAGE-1 mRNA was expressed in Ewing's sarcoma, lung cancer and metastatic melanoma (15,22,23). Recent analysis using a cancer-profiling array showed that XAGE-1 mRNA was expressed in various types of cancer such as breast, lung and prostate cancer (7).…”

“…Four XAGE-1 transcript variants, XAGE-1a, b, c, and d, have been discovered and shown to be expressed in metastatic melanoma and Ewing's sarcoma (15,22,23). By recombinant expression cloning analysis (SEREX), we recently identified XAGE-1b as a dominant antigen recognized by serum from a lung adenocarcinoma patient using an autologous tumor cell line as a source of a cDNA library (1).…”

Activation of human cancer/testis antigen gene, XAGE‐1, in tumor cells is correlated with CpG island hypomethylation

“…7,8 The XAGE-1 gene consists of 4 exons and is located on X-chromosome. Alternative splicing produces 4 different transcripts of XAGE-1 gene in Ewing's sarcoma.…”

“…3,4 Like most cancer/testis antigen family members, the XAGE-1 gene is located on the X-chromosome and is highly expressed in germ cells of the testis but not in other normal tissues. 5,6 Previous studies have shown that XAGE-1 is frequently expressed in Ewing's sarcomas and alveolar rhabdomyosarcomas, 7,8 suggesting that expression of this gene follows a pattern described for other cancer/testis antigen-associated genes.…”