Specific association between alcohol intake, high grade of differentiation and 4q34-q35 deletions in hepatocellular carcinomas identified by high resolution allelotyping.

One of the most frequent deletions in hepatocellular carcinoma (HCC) is that involving the long arm of chromosome 4 (30 to 70% of the cases). These chromosomal deletions are closely related to hepatitis B virus (HBV) infection. A tumor suppressor gene (TSG) located on 4q has been proposed in liver carcinogenesis, but has not been identified as yet.

A new recurrent and specific cryptic translocation, t(5;14)(q35;q32), is associated with expression of the Hox11L2 gene in T acute lymphoblastic leukemia.

FISH identified a cryptic t(5;14)(q35;q32) in T acute lymphoblastic leukemia (ALL), whereas it was not observed in B ALL samples. This translocation is present in five out of 23 (22%) children and adolescents with T ALL tested. RanBP17, a gene coding for a member of the importin beta protein family, and Hox11Like2, an orphan homeobox gene were mapped close to the chromosome 5 breakpoints and CTIP2, which is highly expressed during normal T cell differentiation, was localized in the vicinity of the chromosome 14 breakpoints.

SIAH-1 promotes apoptosis and tumor suppression through a network involving the regulation of protein folding, unfolding, and trafficking: identification of common effectors with p53 and p21(Waf1).

We have previously described biological model systems for studying tumor suppression in which, by using H-1 parvovirus as a selective agent, cells with a strongly suppressed malignant phenotype (KS or US) were derived from malignant cell lines (K562 or U937). By using cDNA display on the K562/KS cells, 15 cDNAs were now isolated, corresponding to genes differentially regulated in tumor suppression. Of these, TSAP9 corresponds to a TCP-1 chaperonin, TSAP13 to a regulatory proteasome subunit, and TSAP21 to syntaxin 11, a vesicular trafficking molecule.

Identification of muscle-specific calpain and beta-sarcoglycan genes in progressive autosomal recessive muscular dystrophies.

The autosomal recessive forms of limb-girdle muscular dystrophies are encoded by at least five distinct genes. The work performed towards the identification of two of these is summarized in this report. This success illustrates the growing importance of genetics in modern nosology.

Activation of the human homologue of the Drosophila sina gene in apoptosis and tumor suppression.

Developmentally regulated genes in Drosophila, which are conserved through evolution, are potential candidates for key functions in biological processes such as cell cycle, programmed cell death, and cancer. We report cloning and characterization of the human homologue of the Drosophila seven in absentia gene (HUMSIAH), which codes for a 282 amino acids putative zinc finger protein. HUMSIAH is localized on human chromosome 16q12-q13.

Isolation of 10 differentially expressed cDNAs in p53-induced apoptosis: activation of the vertebrate homologue of the drosophila seven in absentia gene.

We report the isolation of 10 differentially expressed cDNAs in the process of apoptosis induced by the p53 tamor suppressor. As a global analytical method, we performed a differential display of mRNA between mouse M1 myeloid leukemia cells and derived clone LTR6 cells, which contain a stably transfected temperature-sensitive mutant of p53. At 32 degrees C wild-type p53 function is activated in LTR6 cells, resulting in programmed cell death.

Preferential localization of the limb-girdle muscular dystrophy type 2A gene in the proximal part of a 1-cM 15q15.1-q15.3 interval.

A gene for a recessive form of limb-girdle muscular dystrophy (LGMD2A) has been localized to chromosome 15. A physical map of the 7-cM candidate 15q15.1-q21.

Mutations in the proteolytic enzyme calpain 3 cause limb-girdle muscular dystrophy type 2A.

Limb-girdle muscular dystrophies (LGMDs) are a group of inherited diseases whose genetic etiology has yet to be elucidated. The autosomal recessive forms (LGMD2) constitute a genetically heterogeneous group with LGMD2A mapping to chromosome 15q15.1-q21.

A primary expression map of the chromosome 15q15 region containing the recessive form of limb-girdle muscular dystrophy (LGMD2A) gene.

Previous genetic and physical studies of LGMD2A, an autosomal recessive form of limb-girdle muscular dystrophy, have led to the establishment of a 10-12 Mb YAC contig encompassing the morbid locus. In order to progress toward the identification of the gene involved in LGMD2A, a primary transcription map of this genomic region was generated. The direct cDNA selection strategy was used with three YACs covering the candidate region and two different muscle cDNA libraries.

Regional localization of human chromosome 15 loci.

One hundred forty-nine chromosome 15 loci were mapped by PCR with respect to chromosome breakpoints in three somatic cell hybrids retaining total or part of chromosome 15 and to a 10-Mb YAC contig. This chromosome was subdivided into 5 regions, yielding an average resolution of more than 1 sequence tagged site per megabase. The mapped loci included 18 genes, 60 cDNA-derived sequence tagged sites, and 69 microsatellites.

Mapping of a chromosome 15 region involved in limb girdle muscular dystrophy.

A gene responsible for an autosomal recessive form of limb girdle muscular dystrophy (LGMD2, MIM number 253600) has been localized on chromosome 15. After genotyping additional markers of this chromosome, two were found to flank the disease locus within an interval that was assessed as 7 centiMorgans. The screening of the CEPH YAC libraries with the corresponding probes allowed the isolation of YACs which were used in fluorescence in situ hybridization to define the LGMD2 cytogenetic interval as 15q15.