Nonrandom 4p13 rearrangements of the RhoH/TTF gene, encoding a GTP-binding protein, in non-Hodgkin's lymphoma and multiple myeloma.

We recently isolated the RhoH/TTF gene by its fusion to the LAZ3/BCL6 gene, in a non-Hodgkin's lymphoma (NHL) cell line, which bore a t(3;4)(q27;p11-13) translocation. This gene encodes a novel Rho GTP-binding protein and is specifically expressed in hematopoietic tissues. We made its precise mapping at band 4p13, and described its partial genomic structure. Using fluorescence in situ hybridization and molecular analyses, we report here on the rearrangement of the RhoH/TTF gene, at band 4p13, in four cases of NHL with t(3;4)(q27;p13) translocation and its fusion to the LAZ3/BCL6 gene at band 3q27, in three of these cases. RT-PCR analysis of two cases allowed the detection of variable fusion transcripts emerging from the rearranged alleles, and in one case, a deregulated expression of both RhoH/TTF and LAZ3/BCL6 genes, by promoter substitution, was observed. We also show here another rearrangement of the RhoH/TTF gene in a patient with multiple myeloma and t(4;14)(p13;q32) translocation, with breakage within the IGH gene. It is the first report which describes the recurrent chromosomal alteration of a GTP-binding protein encoding gene, in patients with hematopoietic malignancies.

Germline BRCA1 mutations in patients from 84 families with breast and/or ovarian cancers in northern France.

The BRCA1 gene modification is responsible for an autosomal dominant syndrome of inherited early onset breast and/or ovarian cancer. This gene is estimated to account for almost half of inherited breast cancers and three quarters of inherited breast/ovarian cancers. This suggests that about 1 in every 500 women may carry the BRCA1 mutation. The BRCA1 was isolated by positional cloning in 1994. More than 100 different mutations have been found in the germline of affected individuals. Using systematic sequencing, we looked at BRCA1 germline mutations in 84 patients treated at the Centre Oscar Lambret for breast and/or ovarian cancer who belonged to high-risk families. We found 39 mutations: 22 true mutations inducing modifications of the BRCA1 protein (BRCA1+), six mutations with unknown consequences on the BRCA1 protein, and eleven mutations corresponding to polymorphisms that had been described previously. All the BRCA1+ cases had a HPG3 tumour. The median age of discovery and the receptor positivity percentage are lower in hereditary breast cancer than in the standard population of the breast cancers treated in our centre. Conversely, most of the BRCA1+ patients are without node involvement. This shows that BRCA1 mutations are not always related to parameters thought to indicate a bad prognosis.

Large-cell medulloblastoma with arrestin-like protein expression.

We report a case of a cerebellar large-cell medulloblastoma in a 12-year-old patient. Despite a gross-total resection followed by a radiation therapy and then a chemotherapy, the death occurred 6 months later. The cyogenetic analysis showed an isochromosome 17q. Immunoreactivity for synaptophysin, neurofilaments, chromogranin and arrestin-like proteins was detected, whereas rhodopsin, vimentin, EMA and PAX-6 were negative. In this study, we demonstrate that large-cell medulloblastoma with translocation in chromosome 17q is a neuronal differentiated medulloblastoma with non-photoreceptor characterization. By reverse transcription and polymerase chain reaction (RT-PCR) method, using primers for beta1, beta2 and visual arrestin, we demonstrate corresponding mRNA for beta1, beta2 arrestin but not for visual arrestin. These results suggest that arrestin immunoreactivity in this tumor corresponds to non-visual arrestin. This case corresponds to a new entity of large-cell medulloblastoma. The potential role of a new marker linked to a beta2 adrenergic receptor needs further molecular characterization to be useful.

Evaluation and use of the white blood cell differential provided by the Coulter STKS in a children's hospital.

The Coulter STKS was evaluated in a children's hospital, in order to (a) compare the WBC differential given by the instrument to a 400 cell visual differential (reference method); (b) evaluate the sensitivity and specificity of the alarm system, and (c) provide data concerning the use and interpretation of results in children. 653 blood samples were collected. The Coulter STKS results were studied in 523 patients having no morphological abnormalities in the blood smears, separated into subgroups according to the presence of STKS alarms and according to age. The results were found accurate both in STKS negative and STKS positive patients (i.e., those with alarms: 'Blasts', Imm Gran 2, Variant Lymph, NRBC, review slide). Negative STKS results had the same accuracy in all age groups, except in neonates where slide review must be systematically performed. The instrument exhibited a good sensitivity of the suspect flags studied (91.4%), with a lower specificity (72%) reflecting the number of false positive results found in our group, probably due to the cytological features particular to children. However, it was shown that the numerical results given by the Coulter STKS in positive patients could be taken into account, provided that a scan of the blood smear was negative for morphological WBC abnormalities.