Virginia L. Bertness

T-Cell Receptor Gene Rearrangements as Clinical Markers of Human T-Cell Lymphomas

The ability to detect immunoglobulin-gene rearrangements has proved useful in confirming diagnoses of suspected B-cell lymphomas and in establishing their monoclonality. By analogy, we employed a cloned DNA probe for the beta chain of the T-cell receptor gene to determine whether gene rearrangements were present in human T-cell neoplasms representing various stages of T-cell development. Gene rearrangements were present in all cases of T-cell disorders except a single case of T gamma lymphocytosis, a disorder that has not been proved to be a clonal T-cell neoplasm. A germline gene configuration was present in all patients with non-T-cell neoplasms and in normal tissues from patients with T-cell lymphoma. The probe promises to be useful for confirming the pathological an immunologic diagnosis in difficult cases of T-cell disorders and for assessing the extent of disease.

The SIL gene is required for mouse embryonic axial development and left-right specification

The establishment of the main body axis and the determination of left–right asymmetry are fundamental aspects of vertebrate embryonic development. A link between these processes has been revealed by the frequent finding of midline defects in humans with left–right anomalies. This association is also seen in a number of mutations in mouse and zebrafish,, and in experimentally manipulated Xenopus embryos. However, the severity of laterality defects accompanying abnormal midline development varies, and the molecular basis for this variation is unknown. Here we show that mouse embryos lacking the early-response gene SIL have axial midline defects, a block in midline Sonic hedgehog (Shh) signalling and randomized cardiac looping. Comparison with Shh mutant embryos, which have axial defects but normal cardiac looping, indicates that the consequences of abnormal midline development for left–right patterning depend on the time of onset, duration and severity of disruption of the normal asymmetric patterns of expression of nodal, lefty-2 and Pitx2 .

The human galactosyltransferase gene is on chromosome 9 at band p13

The structural gene for galactosyltransferase (glycoprotein 4-B-galactosyltransferase, EC 2.4.1.38) was localized to human chromosome 9 band p13 by chromosome in situ hybridization using a cloned bovine galactosyltransferase cDNA probe. This chromosomal location is at the same position to which galactose-1-phosphate uridyltransferase, an enzyme which provides the nucleotide sugar substrate (UDP-galactose) for galactosyltransferase, has been mapped.

Characterization of the breakpoint of a t(14;14)(q11.2;q32) from the leukemic cells of a patient with T-cell acute lymphoblastic leukemia

The leukemic cells and derivative cell line from a 74-year-old male with T-cell acute lymphoblastic leukemia showed chromosomal abnormalities including a t(14;14)(q11.2;q32). This translocation is characteristic of a variety of T-cell malignancies, particularly T-cell prolymphocytic leukemia and the clonal proliferations of peripheral T cells in patients with ataxia-telangiectasia. Using DNA probes that spanned the T-cell receptor alpha chain (TCRA) joining (J) locus, the DNA rearrangement caused by the translocation was identified, cloned, and sequenced. The breakpoint shows site-specific juxtaposition of a TCRA joining segment and DNA from a region of 14q32 centromeric to the immunoglobulin heavy chain locus. Comparison of restriction map and nucleotide sequence from this translocation with other related chromosomal breakpoints suggests a dispersion of breakpoints throughout the 14q32 region.

Human gastrin-releasing peptide gene maps to chromosome band 18q21

A complementary DNA clone encoding human pre-pro gastrin-releasing peptide, a 27-amino acid neuropeptide and putative growth factor, was used to determine the chromosomal location of this gene. Southern blot hybridization to genomic DNA isolated from a panel of human-rodent somatic cell hybrids unambiguously maps this gene to human chromosome 18. In situ chromosomal hybridization confirms the hybrid data and further localized the gene to chromosome band 18q21. Karyotypic abnormalities in tumors and inherited disease states which involve chromosome band 18q21 may now be studied for correlated changes in the structure and expression of the human GRP gene.