Identification of differentially expressed genes in hepatocellular carcinoma and metastatic liver tumors by oligonucleotide expression profiling.

BACKGROUND: The characterization of differentially expressed genes between cancerous and normal tissues is an important step in the understanding of tumorigenesis. Global gene expression profiling with microarrays has now offered a powerful tool to measure the changes of thousands of genes in any carcinoma tissues in an effort to identify these key disease-related genes. To compare the gene expression of a primary liver carcinoma, metastatic carcinoma to the liver, and normal liver, the authors analyzed tissue from six primary hepatocellular carcinomas (HCCs), five colorectal adenocarcinoma metastases to the liver, and eight normal livers. METHODS: Samples were processed from total RNA to fragmented cRNA and hybridized onto Affymetrix GeneChip(R) expression arrays. Analyses were performed to determine the consensus pattern of gene expression for primary liver carcinoma, metastatic liver carcinoma, and normal liver tissue and their changes in expression level. RESULTS: In hepatocellular carcinoma, 842 genes were overexpressed, and 393 genes were underexpressed in comparison with genes of normal liver tissue. Of note, 7 of the 20 most increased identified known genes previously have been associated with liver carcinoma or other types of cancers. The 13 additional identified genes until now have not previously shown strong association with cancers. Furthermore, the authors identified 42 genes and 24 expressed sequence tags that are expressed at a significant level in both HCC and metastastic tumors, presenting a list of marker genes indicative of cancerous liver tissue. CONCLUSIONS: In this study, genes that can be involved in the production of and maintenance of hepatic carcinomas were identified. These data offer new insight into genes that are potentially important in the pathogenesis of liver carcinoma, as well as additional targets for new strategies for cancer therapy and treatment.

Split hand/split foot malformation with hearing loss: first report of families linked to the SHFM1 locus in 7q21.

Developmental anomalies of the appendicular skeleton are among the most common and easily ascertained birth defects. Split hand/split foot malformations, distinctive in having deficiency of the central rays, occur as isolated anomalies and as one component of multisystem syndromes. The clinical and molecular characterization of a new syndrome, found in two unrelated families, consisting of split foot with hearing loss, is presented here. As in other split hand/split foot conditions, variable expression and reduced penetrance is notable. In the larger family, variably expressed split foot malformations were found in 6 of 11 gene carriers. and mild-to-moderate sensorineural hearing loss in 4. Split hand and cleft lip/palate in one individual and tibial deficiency in another suggest that these malformations are uncommon components of the syndrome. Ectodermal abnormalities did not occur. In the second family, variable split foot was observed in 3 of 4 gene carriers, and sensorineural deafness was present in 3. Split hand was only seen in a gene carrier who also had split foot and deafness. One gene carrier only had deafness. The gene for split hand split foot with sensorineural hearing loss was linked to markers in 7q21 in both families, with a combined (maximum LOD score of 4.37 at theta = 0.0 for locus D7S527) at 80% penetrance. Efforts to identify the responsible gene have not yet been successful.