Racial Disparities in MiT Family Translocation Renal Cell Carcinoma

Abstract

Racial disparities have been documented in the biology and outcome of certain renal cell carcinomas (RCCs) among Black patients. However, little is known about racial differences in MiT family translocation RCC (TRCC). To investigate this issue, we performed a case-control study using data from The Cancer Genome Atlas (TCGA) and the Chinese OrigiMed2020 cohort. A total of 676 patients with RCC (14 Asian, 113 Black, and 525 White) were identified in TCGA, and TRCC was defined as RCC with TFE3/TFEB translocation or TFEB amplification, leading to 21 patients with TRCC (2 Asian, 8 Black, 10 White, and 1 unknown). Asian (2 of 14 [14.3%] vs 10 of 525 [1.9%]; P = .036) and Black (8 of 113 [7.1%] vs 1.9%; P = .007) patients with RCC showed significantly higher prevalence of TRCC compared with White patients with RCC. The overall mortality rate of TRCC was slightly higher in Asian and Black patients compared with White patients (HR: 6.05, P = .069). OrigiMed2020 Chinese patients with RCC had a significantly higher proportion of TRCC with TFE3 fusions than TCGA White patients with RCC (13 of 250 [5.2%] vs 7 of 525 [1.3%]; P = .003). Black patients with TRCC were more likely to exhibit the proliferative subtype than White patients (6 of 8 [75%] vs 2 of 9 [22.2%]; P = .057) for those who had RNA-seq profiles. We present evidence of higher prevalence of TRCC in Asian and Black patients with RCC compared with White patients and show that these tumors in Asian and Black patients have distinct transcriptional signatures and are associated with poor outcomes.

Silencing of genes by promoter hypermethylation shapes tumor microenvironment and resistance to immunotherapy in clear-cell renal cell carcinomas

“… 6 To assign each ccRCC case to one of the seven subtypes, we employed the nearest template prediction (NTP) approach, as previously described. 66 , 83 This method uses the gene expression profiles of the samples and compares them to predefined templates corresponding to each subtype, enabling accurate classification.…”

Racial Disparities and Molecular Insights in Translocation Renal Cell Carcinoma: Advancing Understanding and Treatment Approaches

“…The study conducted by Lu et al significantly contributes to the existing knowledge on tRCC by examining how race may influence the susceptibility to tRCC and how distinct transcriptomic profiles among different races may explain variations in tRCC prognosis. 11 This retrospective cohort study utilized data from The Cancer Genome Atlas (TCGA) and an independent validation cohort from the Chinese pan-cancer cohort. By leveraging the genomic data from these cohorts, the investigators were able to identify patients harboring translocations or copy number variants in MIT -family genes which classified them as patients with tRCC, even though many of whom were initially misclassified in the dataset.…”