Abstract Purpose: Papillary renal cell carcinoma type2 (PRCC2) is 2nd most common kidney malignancy followed by clear cell renal cell carcinoma (CCRCC). PRCC2 has poor prognosis, treatment strategy is not established and the genetic alteration is poorly understood. We sequenced PRCC2 samples using custom-made kidney cancer panel to figure out genetic alterations of PRCC2. Methods: We have reviewed publications about the genetics of kidney cancer including all subtypes and selected 55 candidate genes. This cancer panel consisted of 1022 regions by Agilent SureSelect Target Enrichment. We sequenced 12 PRCC2 tumor samples along with 6 paired normal tissue samples. The patients' age were ranged from 26 to 82 year-old, and 3 patients were female (25%). Genomic DNA was isolated from dissected tumor tissue samples (6 fresh, frozen and 6 formalin-fixed, paraffin-embedded) and normal tissue samples. Sequencing was performed by Illumina platform and aligned to H. sapiens, hg19, GRCh37. Total probe number was 4103 and size was 283.494 kbp. Presumed germline variants, which were present in matched normal tissue, were filtered out, and manual curation was performed for each area of variants. Results: Fifty-four of 55 target genes had 100% coverage, in spite of 92.7% coverage of one target gene. We found two novel FH mutations (one single nucleotide variant and one 5bp indel) and one novel NFE2L2 mutation. Two out of 12 samples (17%) were altered in NRF2 pathway (1 NFE2L2 and 1 KEAP) which was already well-known as driver in PRCC2. Novel PBRM1 mutation in two samples and SETD2 mutation in one sample were identified. In addition, PTEN, TSC1, KDM5C and AKT1 mutation are observed in one case, respectively. No VHL mutation in PRCC2 was revealed. Conclusions: We analyzed somatic mutation of PRCC2 with custom-made kidney cancer panel. We found several candidate driver mutations of PRCC2. Our result reveals that the genetics of PRCC2 is heterogeneous, therefore, the approach using kidney cancer panel could be used to characterize individual PRCC2. The gene list of RCC panelABCB1BRAFERBB2MDM2NUDT11SDHBTP53ABL1CNTNAP4FHMDM4PBRM1SDHCTSC1AKR1B10CR1FLCNMETPCDHGA8SDHDTSC2AKT1CUL3HIF1AMTORPIK3CASTED2VEGFAALKDACH2KANK3MYCPOTECSIRT1VHLANKRD36EBPLKEAP1NBPF10PTENSPAM1WDR52ARID1AEGFRKRASNFE2L2RETSTAG3L2TSC1BAP1EPAS1KRT1NPNTROS1TERT Citation Format: Ji-Yeon Kim, Se-Hoon Lee, Jong-Il Kim, Jong-Yeon Shin, Dae seog Heo. Target sequencing of papillary renal cell carcinoma, type 2, using custom-made kidney cancer panel. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1888. doi:10.1158/1538-7445.AM2014-1888