African-American patients with biopsy-proven obesity-related NAFLD and NASH have a specific hepatic gene expression pattern that may explain their differences from Caucasian patients with NAFLD in developing progressive liver disease.

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Frequent loss of heterozygosity (LOH) on human chromosome 7q31 has been reported in numerous malignancies. Suppressor of tumorigenicity 7 (ST7) has been identified as a candidate tumor suppressor gene in this region. To identify whether 7q31 and genetic alterations of ST7 were involved in human esophageal carcinogenesis, we performed LOH mapping of a 5.4 cM region at 7q31-q35 in 43 primary esophageal carcinomas, as well as mutational analyses of the ST7 gene in tumors with LOH in this region. Of 43 tumors, 12 (28%) showed LOH at 7q31-q35. These included four (22%) of 18 squamous cell carcinomas and eight (32%) of 25 adenocarcinomas. The peak LOH locus was D7S480, lying 4.2 Mb telomeric to ST7 and showing LOH in eight of 37 informative tumors, or 22%. No mutations were found in the entire coding or flanking intronic regions of the ST7 gene among 12 tumors with 7q-LOH. In addition, quantitative RT-PCR analyses of ST7 mRNA expression levels in 11/13 normal-tumor pairs failed to show more than a 50% decrease in tumor ST7 mRNA relative to matched normal tissues. These data suggest that LOH at 7q31-q35 is involved in the origin or progression of at least a subset of esophageal carcinomas, but that ST7 is not the target gene of this somatic event.Oncogene ( Esophageal carcinoma is one of the most common cancers worldwide, with a very poor prognosis and a marked increase in prevalence in developed countries (Miller et al., 1996). To make inroads against this deadly disease, it will be critical to clarify carcinogenic pathways underlying it, including the inactivation of tumor suppressor genes (TSGs). Several abnormalities have been reported in esophageal cancer, notably including frequent p53 mutation and loss of heterozygosity (LOH) involving numerous chromosomal arms (Hollstein et al., 1990;Shibagaki et al., 1994;Riegman et al., 2001;Roth et al., 2001).Chromosomal arm 7q31 has been implicated as a TSG site because of frequent LOH at this locus in a variety of tumors of epithelial origin (Liang et al., 1998;van Dekken et al., 1999, Zenklusen et al., 1994b, 1995. Furthermore, introduction of a single chromosome 7 inhibited the tumorigenicity of a mouse squamous cancer cell line (Zenklusen et al., 1994a). Lately, Zenklusen et al. reported that suppressor of tumorigenicity 7 (ST7) is a candidate TSG at 7q31, showing frequent mutation in colon and breast cancers. They also demonstrated that the introduction of exogenous wild-type ST7 cDNA suppresses the in vivo tumorigenicity of PC3, a human prostate cancer cell line with LOH at 7q31 (Zenklusen et al., 2001). Since ST7 is also expressed in the normal esophagus (Zenklusen et al., 2001), we assumed that this gene might be involved in the development of esophageal cancer. Thus, we conducted LOH mapping of 7q31-q35 in esophageal cancers, tested LOH-positive tumors for somatic sequence alterations of the ST7 gene, and analysed ST7 mRNA expression levels in a subset of primary tumors.LOH mapping was performed on 43 paired normal and tumorous esophageal tissues, consisting of 18 ...