Changes

Renal cell tumors:

Renal cell tumors:

1. Clear cell renal carcinoma (~65%)

#Clear cell renal carcinoma (~65%)

2. Multilocular cystic renal neoplasm of low malignant potential

#Multilocular cystic renal neoplasm of low malignant potential

3. Papillary renal carcinoma (~20%)

#Papillary renal carcinoma (~20%)

4. Hereditary leiomyomatosis and renal cell carcinoma (RCC) syndrome–associated RCC

#Hereditary leiomyomatosis and renal cell carcinoma (RCC) syndrome–associated RCC

5. Chromophobe renal carcinoma (~5%)

#Chromophobe renal carcinoma (~5%)

6. Collecting duct carcinoma

#Collecting duct carcinoma

7. Renal medullary carcinoma

#Renal medullary carcinoma

8. MiT family translocation carcinomas

#MiT family translocation carcinomas

9. Succinate dehydrogenase [SDH]–deficient renal carcinomas

#Succinate dehydrogenase [SDH]–deficient renal carcinomas

10. Mucinous tubular and spindle cell carcinoma

#Mucinous tubular and spindle cell carcinoma

11. Tubulocystic renal cell carcinoma

#Tubulocystic renal cell carcinoma

12. Acquired cystic disease–associated renal cell carcinoma

#Acquired cystic disease–associated renal cell carcinoma

13. Clear cell papillary renal cell carcinoma

#Clear cell papillary renal cell carcinoma

14. Renal cell carcinoma, unclassified

#Renal cell carcinoma, unclassified

15. Papillary adenoma

#Papillary adenoma

16. Oncocytoma (~5%)

#Oncocytoma (~5%)

 

Recent studies of The Cancer Genome Atlas (TCGA) on three major histologically defined types of RCC—clear cell, papillary, and chromophobe – showed that molecular subtypes exist within each major RCC type, and these subtypes have distinct driver mutations, unique dysregulated molecular pathways, varying clinical course, different responses to therapy, and patient survival.  In addition, Specific molecular aberrations could be identified in more than one RCC type. Widespread molecular changes associated with TFE3 gene fusion or chromatin modifier genes were present within a specific subtype and spanned multiple subtypes as shown, for example, that these alterations were found in a subset of both clear cell and papillary RCC. There were differences in patient survival and in alteration of specific pathways, including hypoxia, metabolism, MAP kinase, NRF2-ARE, Hippo, immune checkpoint, and PI3K/AKT/mTOR. Presumed actionable alterations include PI3K and immune checkpoint pathways. Therefore, therapeutic strategies could be tailored to each RCC disease subset, based on their molecular subtypes.

Recent studies of The Cancer Genome Atlas (TCGA) on three major histologically defined types of RCC—clear cell, papillary, and chromophobe – showed that molecular subtypes exist within each major RCC type, and these subtypes have distinct driver mutations, unique dysregulated molecular pathways, varying clinical course, different responses to therapy, and patient survival.  In addition, Specific molecular aberrations could be identified in more than one RCC type. Widespread molecular changes associated with TFE3 gene fusion or chromatin modifier genes were present within a specific subtype and spanned multiple subtypes as shown, for example, that these alterations were found in a subset of both clear cell and papillary RCC. There were differences in patient survival and in alteration of specific pathways, including hypoxia, metabolism, MAP kinase, NRF2-ARE, Hippo, immune checkpoint, and PI3K/AKT/mTOR. Presumed actionable alterations include PI3K and immune checkpoint pathways. Therefore, therapeutic strategies could be tailored to each RCC disease subset, based on their molecular subtypes.