Polyphosphates as a source of enhanced P fluxes in marine sediments overlain by anoxic waters: Evidence from 31P NMR

We examined loss of heterozygosity (LOH) for two loci on chromosome 17p (D17S5 and TP53), and erbB-2 gene amplification, in primary breast cancers from 67 Brazilian patients. We identified two distinct regions of LOH on chromosome 17p, one spanning TP53 and the other a more telomeric region (D17S5). Based on a short-term follow-up, Kaplan-Meier analyses of patients' disease-free survival showed that patients with LOH for D17S5, but retaining heterozygosity for TP53, were at higher risk of recurrence (P = 0.007) than those who retained heterozygosity for D17S5. Bivariate analyses indicated that patients with LOH for D17S5 alone had an increased risk of recurrence (hazard ratio = 7.2) over patients with erbB-2 amplification (hazard ratio = 3.7), when compared with patients with neither alteration (hazard ratio = 1.0). Further, lymph node-positive patients whose tumours had both LOH for D17S5 and erbB-2 gene amplification had a higher risk of recurrence than patients whose tumours had neither of these genetic alterations. Our data confirm previous reports of a putative tumour-suppressor gene, distinct from TP53, on distal chromosome 17p which is associated with breast cancer. They further suggest that LOH for loci in this region may provide an independent indicator to identify patients with poor prognosis. Several tumour-suppressor genes that may contribute to breast cancer tumorigenesis are located on chromosome 17, Loss of heterozygosity for loci on chromosome 17p has been reported in 40-60% of sporadic breast carcinomas Andersen et al., 1992). Frequently, these genetic alterations include the tumour-suppressor gene TP53. Mutations of this gene have been identified in 20-40% of sporadic primary breast tumours (Coles et al., 1992; Mazars et al., 1992) as well as in the germline of some patients with Li-Fraumeni syndrome, an inherited cancer syndrome associated with breast cancer (Malkin et al., 1990). However, the frequency of TP53 point mutations in breast tumours is significantly less than the frequency of LOH detected for loci on distal chromosome 17p (Chen et al., 1991; Mazars et al., 1992). Further, Coles et al. (1990) have demonstrated two independent regions of allelic loss on chromosome 17p in breast tumours, one spanning TP53 and the other involving a more telomeric region, implying the existence of another tumour-suppressor gene distal to TP53. Previous studies correlating chromosome 17p LOH with clinicopathological variables in breast cancer have generally failed to distinguish between events at TP53 and at the more distal locus (B0rrensen et al., 1990; Cropp et al., …