FIGURE 4.

Mutational analysis of the UOK276 cell line. (A) Mutation analysis identified a heterozygous missense mutation of TP53 (c.577 C>T, p.H193Y) in the sarcomatoid region of the tumor that was not present in the chromophobe region of the tumor nor the germline DNA of the patient. This mutation was homozygous in the UOK276 cell line. (B) Mutation analysis identified a deletion/insertion mutation of TRAF7 that removed 33 bp containing the end of exon 2 and the beginning of intron 2 and replaced 12 bp, resulting in the loss of 4 amino acids and retention of the last two amino acids of the exon and the canonical splice site. This mutation was present heterozygously in the germline DNA of the patient and in the chromophobe region of the tumor, but demonstrated loss of heterozygosity in the sarcomatoid region of the tumor and in UOK276. Somatic mutation within this gene have been reported in several different kidney cancer types and these are mapped to the functional domains of TRAF and, although no mutations have been observed in the RING finger and TRAF N-terminal domains, mutation of one of the tryptophan-aspartic acid repeat (WD) domains has been reported. ChRCC, chromophobe RCC; CCRCC, clear cell RCC; PRCC, papillary RCC; C.L., cell line.