Prognostic value of loss of chromosome 10q in patients with localized renal cell carcinoma.

626 Background: Several tumor-suppressor genes have been mapped to chromosome 10q, including PTEN. While loss of 10q is a frequently seen cytogenetic abnormality noted to occur in patients with renal cell carcinoma (RCC), little is known about its prognostic significance. We investigated the association of loss of 10q with pathological features and disease-free survival (DFS) in patients with localized RCC. Methods: All patients from UCLA with primary localized RCC who had tumor cytogenetic analysis were included. Alterations in chromosome 10q was specifically reviewed for this study. Logistic regression analyses were used to assess association of loss of 10q with ISUP grading, and T-stage. Cox proportional hazard modeling and Kaplan-Meier analyses were used to assess the impact of loss of 10q on DFS and OS. Recurrence was defined as any local recurrence or development of new metastasis after surgery. Results: A total of 886 patients were included in this study. Loss of 10q occurred in 68 (7.7%) patients and was more commonly seen in chromophobe subtype (24% vs. 6% in non-chromophobe RCC, p < .0001). Loss of 10q was associated with greater tumor size (mean 6.3 vs 5.1 cm, OR = 1.085 [1.024-1.150], p = .008), T3-stage (37% vs 23%, OR = 1.99 [1.17-3.39], p = .011), and ISUP 3-4 (61% vs 37%, OR = 2.64 [1.58-4.40], p < .0001). On survival analysis, after a mean follow-up of 55 months, these patients had a shorter time to recurrence (Log-rank p = .026) and a worse DFS (HR = 2.15 [1.32-3.50], p = .002) than those without loss of 10q. These findings were confirmed on clear-cell RCC subgroup with also a worse OS (HR = 2.00 [1.09-3.67], p = .026) with an estimated 34% risk of death at 5 years for patients with loss of 10q. Conclusions: Loss of chromosome 10q is a prognostic factor associated with larger tumor size, higher grade and T-stage, and worse survival in patients with localized RCC. Identifying patients with loss of 10q can provide additional prognostic information to clinicopathologic variables.

Evidence for the founder effect of RET533 as the common Greek and Brazilian ancestor spreading multiple endocrine neoplasia 2A

Objectives About one-quarter of patients with medullary thyroid cancer (MTC) have inherited disease due to mutations in the RET gene. A rare mutation in exon 8 (G533C) of RET, previously described in a large Brazilian family with MEN2A, also appeared to be clustering in Greece, whereas it was rarely reported in other ethnic groups. The aim of this study was to identify a possible common ancestry between these carriers. Patients and methods Twelve RET G533C mutation carriers, four randomly selected from the Brazilian cohort and eight from apparently unrelated Greek families, were studied for a possible common ancestral origin. RET flanking microsatellite markers at chromosome 10q (D10S197, D10S196, D10S1652 and D10S537) were used. Results Genomic DNA analysis using these markers showed that many of these apparently unrelated individuals shared a common haplotype indicating a common ancestral origin. Conclusion Our data suggest that Brazilian and Greek patients with MTC carrying the G533C mutation in exon 8 of RET gene originate from a common ancestor. Due to historical reasons, we speculate that the more plausible explanation for the origin of this mutation is in Greece.

An Interstitial Deletion at 10q26.2q26.3

We present a case of an interstitial subtelomeric 10q26 deletion in a male child with moderate developmental delay and minor dysmorphic features. Using array comparative genomic hybridization (CGH) and fluorescencein situhybridization (FISH), we have detected an interstitial deletion at 10q26.2q26.3 encompassing a 5.8 Mb region and spanning 24 genes. Interestingly, losses of this chromosome 10 region have not been previously associated with a phenotype outcome. According to anin silicoevaluation, we have suggested thatPPP2R2DandBNIP3losses are likely a cause of developmental delay in the index patient. Our data allow to speculating that haploinsufficiency of these two genes in 10q26.3, which is usually ignored in the context of chromosome 10q deletions, has a phenotypic effect.