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Turning to a large whole-genome-sequenced tumor cohort, researchers analyzed the genomic differences between primary and metastatic cancers. They found that genomic differences between them were modest except in advanced breast, prostate, thyroid, and kidney renal clear-cell carcinomas and pancreatic neuroendocrine tumors. The researchers showed that one in four patients carries the risk of a genetic immune escape event, primarily from loss of heterozygosity of HLA-I., (©2023 American Association for Cancer Research.)

Clear cell renal cell carcinoma (CCRCC) is characterized by mutation of the VHL gene and loss of a segment of chromosome 3. A new study using multi-region exome sequencing has identified substantial intratumoral heterogeneity within large primary CCRCCs, which has profound implications for understanding tumor evolution and for developing effective therapies.

Two recent studies describe the largest molecular profiling analyses to date of clear-cell renal cell carcinoma (ccRCC) and report remarkably similar findings. The recurrent pathway alterations identified in these studies open new avenues for therapeutic advances in this chemotherapy- and radiation-resistant disease.