Abstract 75: Patient-specific genomic profiling for advanced cancers in young adults
Authors: Cha Soojin , Lee Jeongeun , Shin Jong-Yeon , Kim Ji-Yeon , Kim Jong-Il , Lee Se-Hoon 
Published: August 2015

Abstract
Purpose: Large-scale cancer genome analyses have uncovered the genetic landscape of common cancers. However, rate tumor types in adolescent, young adult (AYA) have not been well-characterized genetically. We performed a pilot study of patient-specific cancer genome analysis to know whether we can analyze individual cancer genome without the existing large-scale genomics data of same tumor types in advanced and rare AYA tumors.
Methods: The patients were prospectively enrolled from a medical oncology clinic in a university hospital. Tissue samples of the study patients were acquired from the fresh tissue, formalin-fixed paraffin-embedded (FFPE) tissue and cancer cells from pleural effusion as well. Cancer genome data was acquired using massive parallel sequencing technique from seven AYA patients with advanced solid tumors. WES and WTS data were generated from 6 tumors with matched normal and 4 tumors, respectively. Somatic alterations of cancer genome were classified with 2 distinct categories with heuristic ways and level 1 to 3 depends on differences of genetic alterations based on clinical and biological relevance, and mutation context.
Results: Each different tumor types of 7 study patients were as follows; atypical prostate cancer (AYA01, 30 years old), olfactory neuroblastoma (AYA02, 30 years old), tongue cancer (AYA04, 33 years old), urachal carcinoma (AYA06, 32 years old), germ cell tumor (AYA07, 21 years old), lung cancer (AYA09, 34 years old) and liposarcoma (AYA10, 33 years old). Patients with GCT and tongue cancer had higher mutation rate based on WES data; 476 and 97 non-synonymous somatic nucleotide variations respectively. However, there were only 13∼16 non-synonymous somatic nucleotide variations and 7∼18 indel somatic variations in patients with other four cancers. We identified one level-1 (strong) oncogenic alterations and eight level-1 tumor suppressor alterations as well as 19 level-2 (moderate) and level-3 (modest) alterations were found from 5 WES data (we excluded 1 hypermutated germ cell tumor sample). Some level-1/2 alterations were considered as targetable by developed or developing drugs. Each tumor was characterized by tumor-unique manner. AYA01 was characterized with concurrent tumor suppressor alterations of RasGAP family genes (NF1 and RASA2), AYA02 with chromosome-level copy number alteration and CDKN2C stopgain mutation, AYA04 with concurrent oncogenic (AMER3) and tumor suppressor (FAT1, LGR6, MSX1) alterations of Wnt signaling, AYA06 with KRAS mutation and AYA09 with a fusion of EML4-ALK.
Conclusion: Our study showed that we can characterize rare AYA tumors with WES or WTS data without pre-existing large-scale genomics data of same tumor types, although there are much hurdles in identifying major driver and/or druggable genetic alterations.
Citation Format: Soojin Cha, Jeongeun Lee, Jong-Yeon Shin, Ji-Yeon Kim, Jong-Il Kim, Se-Hoon Lee. Patient-specific genomic profiling for advanced cancers in young adults. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 75. doi:10.1158/1538-7445.AM2015-75