The allelic loss of chromosome 3p25 with c‐myc gain is related to the development of clear‐cell renal cell carcinoma

Abstract

To explore the role of allelic losses at 3p25 and genetic alterations of chromosome 8, we investigated the relationships between genetic alterations in these chromosomal regions and clinicopathologic findings (such as tumor size and grade), by employing fluorescence in situ hybridization (FISH). Fifty Japanese clear-cell renal cell carcinomas (RCCs) were examined by dual-color FISH using cosmid DNA probes for 3p25.1-25.3 combined with probes for chromosome 3 centromere, 8p12, 8p21.1, 8p21.3, 8p22 and 8q24.12-24.13 (c-myc), and chromosome 8 centromere. Deletion at 3p25.1-25.3 was detected in 38 patients (76%), while 8p12 deletion, 8p21.1 deletion, 8p21.3 deletion, 8p22 deletion and c-myc gain were detected in 23 (46%), 25 (50%), 25 (50%), 25 (50%), and 20 patients (40%), respectively. There was a significant correlation between 8p21.1 deletion, 8p21.3 deletion and 8p21.1 deletion with c-myc gain and tumor grade (p = 0.04, 0.04 and 0.02, respectively). Deletions at 8p21.1 and 8p21.3 with 3p deletion were significantly related to tumor grade; the statistical significance was identical to that of sole 8p deletion with tumor grade. The deletion at 3p25.1-25.3 with c-myc gain showed a significant correlation with tumor size, indicating an association with tumor progression. Our results suggest that the allelic loss of chromosome 3p25 with c-myc gain is related to the development of clear-cell RCC.

Clear cell renal cell carcinoma with smooth muscle stroma

“…Finally, our FISH results showed loss of chromosome 3 or 3p in epithelial cells of all 3 tumors. Previous FISH analyses indicate that sporadic CCRCC harbors monosomy for chromosome 3 and deletion of 3p in 26% to 36% and 45% to 76% of cases, respectively [6][7][8], whereas the loss of large regions of genetic material from chromosome 3 is rare in other types of RCC [6][7][8][9][10].…”

The application of cytogenetics and fluorescence in situ hybridization to fine‐needle aspiration in the diagnosis and subclassification of renal neoplasms

“…33 Accordingly, previous reports have illustrated that in some cases, FISH using bacterial artificial chromosome or cosmid probes can detect deletions in 3p to genetically establish a diagnosis of clear cell RCC. 34,35 In our series, karyotyping and/or FISH was successful in 44 of the 74 cases where a portion of the FNA was submitted for cytogenetic analysis. Specific, abnormal cytogenetic profiles were seen in 27 of these cases and the results were concordant with the cytomorphologic impression of the renal tumor except in 1 unusual case.…”

Upregulation of Far Upstream Element-Binding Protein 1 (FUBP1) Promotes Tumor Proliferation and Tumorigenesis of Clear Cell Renal Cell Carcinoma

“…These genes are involved in cell cycle progression, apoptotic cell death, glycolysis, glutaminolysis, and lipid synthesis. By employing fluorescence in situ hybridization, the deletion at 3p25.1–25.3 with c-myc gain had a significant correlation with tumor size in ccRCC [56]. Furthermore, an in vitro study indicated that c-myc knockdown significantly inhibited ccRCC cell proliferation by arresting the cell cycle in the G0/G1 phase [57].…”