Loss of heterozygosity at chromosome segment Xq25-26.1 in advanced human ovarian carcinomas

Abstract

To determine whether a tumor suppressor gene of importance to epithelial ovarian cancer resides on the X chromosome, we examined loss of heterozygosity (LOH) in 123 epithelial ovarian cancer cases. In 54 such cases, we examined LOH at 26 loci on the human X chromosome. In eight cases, we examined LOH in 14 loci and in 61 cases we examined LOH in 13 loci. Matched DNA samples from tumors and corresponding normal tissues were analyzed by polymerase chain reaction (PCR) amplification of microsatellite markers. Frequent losses were found in epithelial carcinomas at the Xq25‐26.1 region, including DXS1206(34.5% loss in informative cases), DXS1047(27.7%), HPRT(24.1%), and DXS1062 (33.3%). The minimum overlapping region of LOH was approximately 5 megabases (Mb), flanked by DXS1206(Xq25) and HPRT(Xq26.1). The methylation status of the remaining allele of the androgen receptor gene in the tumors exhibiting LOH at the Xq25‐26.1 region suggested that the loss was exclusively in the inactive X chromosome. We next determined whether a significant relationship exists between Xq LOH and other parameters, including histologic grade and/or clinical stage of the tumors and LOH at TP53. The Xq LOH had a significant association with grade 2 to 3 tumors at stages II to IV. Sixteen of 18 cases that showed Xq LOH revealed LOH at the TP53 locus, and 45% of tumors exhibiting LOH at TP53 showed Xq LOH. These results suggest that there may be a tumor suppressor gene or genes which escape inactivation of the X chromosome at Xq25‐26.1, and that the loss of the gene(s) at Xq25‐26.1 is frequently accompanied by loss of the TP53 or loss of another gene on chromosome 17. These losses may contribute to the progression from a well‐differentiated to a more poorly differentiated state or to metastatic aggressiveness. Genes Chromosomes Cancer 20:234–242, 1997. Published 1997 Wiley‐Liss, Inc.

Malignancy-associated X chromosome allelic losses in foregut endocrine neoplasms: further evidence from lung tumors

“…[14][15][16][17] A potential oncosuppressor gene located in this region is the MEF (myeloid elf-1-like factor) gene, an ETS transcription factor located at Xq26.1. 18 In particular, MEF suppresses the tumorigenesis of human nonsmall cell lung carcinoma cell lines A549 both in vitro and in vivo, most likely through the inhibition of matrix metalloproteinases and interleukin-8 gene transcription.…”

Thyrotoxic adenoma followed by atypical hyperthyroidism due to struma ovarii: clinical and genetic studies

“…Noumoff et al observed a del(X)(q11) in the malignant squamous component of an ovarian teratoma (24). Loss of heterozygosity on Xq is a common event in ovarian tumors and contributes to the progression of the tumor to an undifferentiated stage or aggressive behavior (25,26). Chromosome 10 also seems to be involved in the malignant transformation of mature ovarian teratomas (23).…”

Tumor promoting properties of the ETS protein MEF in ovarian cancer

“…MEF is located on Xq26 and has been posited to be a tumor suppressor gene in ovarian cancer, as MEF is contained in a minimal region of allelic loss in loss of heterozygosity studies of advanced stage ovarian cancer (Choi et al, 1997). There is a single report that MEF can act as negative regulator of the A549 lung cancer cell line, as its overexpression inhibited the ability of A549 cells to grow in soft agar and form tumors in nude mice (Seki et al, 2002).…”