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Traditionally, clear cell papillary renal cell carcinoma (ccpRCC) was considered to share similar molecular and histological characteristics with clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC). Here we aimed to identify somatic and germline variants of ccpRCC. For this purpose, we conducted whole-exome sequencing to detect somatic variants in the tissues of 18 patients with pathologically confirmed ccpRCC, who underwent surgical treatment at Fudan University Shanghai Cancer Center. Targeted sequencing was conducted to detect germline variants in paired tumor or normal tissues or blood. Somatic and germline variants of ccRCC and Renal cell carcinoma included in The Cancer Genome Atlas data and other published data were analyzed as well. The molecular profiles of ccpRCC, ccRCC and pRCC were compared. Among the 387 somatic variants identified,  TCEB1  (3/18) and  VHL  (3/18) variants occurred at the highest frequencies. Germline mutation detection showed that nine variants associated with Fanconi anemia (VAFAs) pathway ( FANCA , 6/18;  FANCI , 3/18) were identified in 18 ccpRCC patients. Among ccpRCC patients with VAFAs, five out of eight patients had second primary malignancy or family history of cancer. Somatic variants characteristics may distinguish ccpRCC from ccRCC or pRCC and germline VAFAs may be a molecular characterization of ccpRCC. Compared with ccRCC or pRCC, ccpRCC patients may be significantly correlated with higher risk of developing second primary malignancy.

pathology and oncology research/pathology oncology research

Clear Cell Papillary Renal Cell Carcinoma Shares Distinct Molecular Characteristics and may be Significantly Associated With Higher Risk of Developing Second Primary Malignancy