Abstract 2446: Integrated analysis of somatic mutations in subcutaneous panniculitis-like T-cell lymphoma by whole-exome and -transcriptome sequencing
Authors: Song Hyojin , Koh Youngil , Kim Daeyoon , Yun Hongseok , Sun Choong-Hyun , Im Hogune , Shin Dong-Yeop , Yoon Sung-Soo 
Published: July 2017

Abstract
Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rarely differentiated form of non-Hodgkin lymphoma. This uncommon disease is triggered by preferential lymphoma infiltration into subcutaneous adipose tissue, and nodule formation in the fatty tissue. Consequently, the early stage symptoms of SPTCL is found as multiple subcutaneous nodules beneath the skin. Due to the low incidence rate and indolent progression of the disease, the genetic alterations associated with SPTCL still remains poorly characterized. Genetic profiling of SPTCL by integrated whole-exome and -transcriptome sequencing will augment the comprehensive characterization of somatic mutations in SPTCL. To investigate the genetic alterations associated with the incidence of SPTCL, we performed whole-exome sequencing of both biopsy sample collected from the patient’s left shoulder lesion, and matched saliva sample to 200X and 100X read depth of coverage, respectively. Whole-transcriptome sequencing of the tumor sample was also performed for expression level analysis; gene fusions are also explored by TopHat-fusion-post. Somatic mutations were precisely detected by our internally developed somatic variant caller, which is an adjusted version of VarScan2 with additional filters based on thresholds of p-value and odds ratio. Overall, we discovered a total of 158 somatic variants: 139 SNVs and 19 indels, by using somatic variant detection algorithm of our own. By applying the additional filters to these variants, two genes were remarkably identified: SQSTM1 and BAGE3. SQSTM1 (sequestosome 1), also known as ubiquitin-binding protein p62, encodes proteins that regulate ubiquitination, autophagy, and activation of NFkB1. Through cBioPortal database search, SQSTM1 found to be highly amplified across the various cancer types, such as neuroendocrine prostate cancer (NEPC), kidney renal clear cell carcinoma (RCC), and pancreatic cancer. On the other hand, BAGE3, B melanoma antigen 3, was reported as a candidate gene encoding tumor antigens. Gene fusions were identified by comparing the number of spanning reads and mate pairs, and fusion of NOL7 and RANBP9 on chromosome 6 showed the highest fusion score of 604.45. Comprehensive characterization of the initiation, progression, and relapse of subcutaneous panniculitis-like T-cell lymphoma is yet thoroughly understood. Hence, establishing the genetic basis and profiling the genomic landscape of SPTCL will broaden our understanding of SPTCL, and enhance the therapeutic effectiveness in the pre-diagnosis and treatment of the disease, as well as targeted gene therapies. Furthermore, to strengthen the statistical power of the somatic mutation analysis, we are planning to expand the cohort and conduct functional validation study of selected genes by using secured paraffin blocks of SPTCL patients.
Citation Format: Hyojin Song, Youngil Koh, Daeyoon Kim, Hongseok Yun, Choong-Hyun Sun, Hogune Im, Dong-Yeop Shin, Sung-Soo Yoon. Integrated analysis of somatic mutations in subcutaneous panniculitis-like T-cell lymphoma by whole-exome and -transcriptome sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2446. doi:10.1158/1538-7445.AM2017-2446