Summary Previous work has implicated putative tumour-suppressor (ts) genes at 6q27 and a broad region at 6pl2-q23. Here

S_inmary To define regions of deletion of chromosome 6q in breast cancer, we scored 18 (CA), microsatellites for allelic imbalance (AI) in 42 paired blood/tumour samples. Heterozygosity frequencies of the markers in the sample population ranged from 31% to 92% (mean 68%). Two regions of the chromosome arm showed Al values greater than the background range of 10-22% (mean 17%) of informative cases that was observed with five markers spanning 6q21 -q25.2. Firstly, seven markers gave Al values that averaged 35% in a region flanked by D6S313 (Al = 10%) at 6ql3 and D6S283 (Al = 17%) at 6qI6.3-21. The second region showed marginally increased Al at 6q25.2-q27 and included D6S193, previously shown to be close to a tumoursuppressor gene involved in ovarian carcinoma. Since Al of 6q in breast cancer was shown previously to be due predominantly to loss of heterozygosity, our results suggest the presence of at least two tumour-suppressor genes on 6q that are involved in breast cancer. The proximal region has not been recognised in breast cancer before and is involved in a higher frequency of tumours than the distal region.

Apoptosis has been implicated in the pathogenesis of marrow failure in MDS and the coexistence of marrow hypercellularity along with blood cytopenias was seen as evidence of extreme cell death of mainly mature cells in the marrow (ineffective hematopoiesis). We investigated apoptosis in 53 patients with MDS, by using single-step DNA extraction and gel electrophoresis and then by separating fresh marrow mononuclear cells in CD34+ and CD34 − populations and in situ single cell evaluation of the process. We also studied the expression of apoptosis-related genes, in total and separated mononuclear marrow cells and correlated the findings with clinical and laboratory characteristics. Patients with apoptosis had increased marrow cellularity, longer overall survival and a longer period for transformation to AML. In 'good' prognosis MDS patients, total mononuclear marrow cells, as well as isolated populations of CD34+ and CD34 − cells showed significant degrees of apoptosis; in 'poor' prognosis cases, however, apoptosis was evident only in a large percentage of CD34 + marrow cells and not in total or CD34 − cells. Absence of expression of both c-myc and p53 in total marrow cells was associated with significant degrees of apoptosis and in isolated CD34+ and CD34 − marrow cells the phenomenon was inversely correlated with the level of bcl-2 expression. In conclusion, marrow apoptosis is detected in both CD34+ and CD34 − cells in early MDS and seems to be restricted to CD34+ cells in advanced MDS cases.

We have used fluorescence in situ hybridisation (FISH) with a series of yeast artificial chromosome (YAC) clones that map to the long arm of chromosome 6 (6q) to define the region(s) of deletion in seven cases of non-Hodgkin's lymphoma (NHL), in which a deletion of 6q had been detected by conventional cytogenetics. The FISH analysis detected two regions of deletion: (i) A proximal region flanked by M6P1 (6q14-15) and FYN (6q21), containing D6S246, which was missing in all seven cases. This locus was also found to be deleted in all six cases of acute lymphoblastic leukaemia (ALL) studied previously. (ii) A second region of 6q, which was distal to 6q23.1 (D6S238) and included ESR (6q25.1) and D6S281 (6q27), which was shown to be present in all our cases of ALL, was found to be deleted in 4 of the 7 cases of NHL. Our results support the suggestion that tumour suppressor genes, involved in the pathogenesis of lymphoid malignancies, may be present within these regions.

We have characterised a region of deletion on the long arm of chromosome 6 (6q) in six cases of acute lymphoblastic leukaemia, by fluorescence in situ hybridisation, using a series of YAC clones which map to 6q. Conventional cytogenetic analysis of four of these cases had been interpreted as showing terminal deletions of 6q. We demonstrated by FISH that in all cases the deletions were interstitial. D6S246 (6q16.3) was the only marker which was missing in all six cases, indicating a common region of deletion between the markers M6P1 at 6q14-15 and FYN at 6q21. Our results suggest the presence of a tumour suppressor gene within this interval.