Monosomy of Chromosome 9 Is Associated With Higher Grade, Advanced Stage, and Adverse Outcome in Clear-cell Renal Cell Carcinoma

Abstract

The objective of the study was to evaluate the frequency and the outcomes of whole chromosome 9 loss in 103 patients with clear-cell renal cell carcinoma (ccRCC) using single nucleotide polymorphism-based chromosome microarray analysis. Our study demonstrated that chromosome 9 loss is associated with higher grade, advanced stage, and poor outcome in ccRCC and can potentially be used as a major prognostic predictor in patients with ccRCC. Background: Clear-cell renal cell carcinoma (ccRCC) is one of the most common malignancies in humans and is usually associated with poor outcomes. Cancers are considered to be genetic diseases. Therefore, a better understanding of genetic alterations that are related to disease progression or poor prognosis can help to more precisely identify high-risk patients and treat them more effectively. The aim of this study was to examine the frequency of whole chromosome 9 loss (monosomy of chromosome 9) and its prognostic value in patients with ccRCC. Materials and Methods: Single nucleotide polymorphism-based chromosome microarray (CMA) analysis was performed on 103 resected specimens from patients with ccRCC who had undergone partial or radical nephrectomy between January 2002 and March 2017 at Fox Chase Cancer Center. Monosomy 9 was correlated with clinicopathologic parameters and recurrence-free survival. Results: Chromosome 9 loss was detected in 31 (30%) of 103 tumors. Tumors with chromosome 9 loss had higher histologic grade (3 and 4; P < .001) and pathologic stage (P < .001). In 59 patients with non-metastatic ccRCC, chromosome 9 loss was also associated with higher recurrence rate and shorter recurrencefree survival (RFS) (12-month RFS, 77.8%; 95% confidence interval, 36.5%-93.9% for chromosome 9 loss vs. 95.7%; 95% confidence interval, 84.0%-98.9% for no loss; P ¼ .002). Conclusions: Chromosome 9 loss was found in 30% of patients with ccRCC and correlated with higher grade, advanced stage, and shorter RFS in patients with Stage I to III ccRCC.

K-means clustering of hyperpolarised13C-MRI identifies intratumoural perfusion/metabolism mismatch in renal cell carcinoma as best predictor of highest grade

“…While most other genetic alterations were truncal, the single exception of genetic branching was the LOH of chromosomes 9 and 14, and SETD2 mutation in patient 4, which were all found within the combined medium cluster. Indeed, LOH of chromosomes 9 and 14, as well as elevated genomic intratumoural heterogeneity, have been previously associated with more adverse outcomes [66][67][68] , which supports our suggestion that the medium combined cluster represents the most aggressive intratumoral region. In addition, SETD2 loss has been previously found to promote ccRCC expansion through replication stress and defective DNA damage repair 69 , as well as a switch of ccRCC metabolism towards OXPHOS 70 , in line with our finding of upregulated OXPHOS pathway in the medium combined cluster.…”

Papillary Renal Neoplasm With Reverse Polarity Is Often Cystic

“…Interestingly, we did not find any chromosome imbalances in any of our 7 cases by CMA, a single-nucleotide polymorphism-based microarray technology that identifies DNA copy number imbalances (chromosome gains and losses), but cannot detect balanced genomic alterations (reciprocal translocations, inversions, balanced insertions) or point mutations. [23][24][25] However, our study also included analyses with the TruSight RNA Pan-Cancer panel, which did not reveal any fusion genes. Overall, 30/44 (68%) cases had no chromosome abnormalities, whereas 12/44 (27%) cases had gain(s) of chromosome 7 and/or 17, and 2/44 (4.5%) had showed only loss of the Y chromosome.…”