Abstract 4154: The emerging clinical relevance of genomic profiling medicine in neuroendocrine tumors
Authors: Sonmezler Ozge , Guney Isa B. , Mujde Cem , Bisgin Atil 
Published: September 2020

Neuroendocrine tumors (NET) can develop everywhere in the body which have heterogeneous origins and complicated histology. Thus, genomic profiling becomes inevitable to overcome the disease's complexity through the determination of hereditary predisposition and treatment actionability. For this purpose, next generation sequencing as the most reliable methodology for both germ-line and somatic studies, can be utilized in clinical oncology as we present in this study which liquid biopsy, FFPE tissue and peripheral blood samples in terms of actionability and predisposition for various types of neuroendocrine tumors have been analyzed. A customized multi-gene panel (consists of SDHB, SDHC, CDC73, CASR, PDGFRA, SDHA, RET, SDHAF2, MEN1, SDHD, MAX and PRKAR1A genes) have been used from 3 liquid biopsy, 6 FFPE tissue and 26 peripheral blood samples of 35 distinctive NET patients. Quality control and bioinformatics analysis were performed using QCI-Analyze and QCI-Interpret. Three liquid biopsy and 6 FFPE samples were evaluated for somatic analysis while 26 peripheral blood samples were included in germ-line pipeline. Five (55.6%) of the 9 patients that were studied for somatic changes carry actionable mutations related to therapy sensitivity. While through the germ-line studies, we observed 50% positivity rate for disease predisposition in germ-line studies with sixteen variants in 13 patients. Variant classification criteria were given in details in Table 1 according to the ACMG (American College of Medical Genetics) Standards and Guidelines. Genomic profiling medicine as the emerging area of clinical oncology in this era becomes crucial for disease and patient management properly in terms of a precise approach especially in rare diseases including the rare cancers such as NETs. Most notably, our study emphasizes the relevance of distinctive biological samples in the use of genetic testing for cancer care.

Table 1.Implemented variant classification criteria of detected germ-line mutations in our study.PatientGeneVariant (amino acid change)ACMG criteria (doi: 10.1038/gim.2015.30)P1KITM541L (Heterozygote)PM2, BP4, BP6P2SDHCR72H (Heterozygote)PM1, PM2, PP3P3SDHBG19FS*57 (Heterozygote)PVS1, PM1, PM2P4PDGFRAS66R (Heterozygote)PM2, BP1, BP4P5RETA96V (Heterozygote)PM2, PP2, BP4P6KITR946* (Heterozygote)PM2, PP2, BP4P7RETG691S (Heterozygote)PP2, BA1, BS3, BP4P8RETG691S (Heterozygote)PP2, BA1, BS3, BP4P9RETG691S (Heterozygote)PP2, BA1, BS3, BP4P10RETG691S (Heterozygote)PP2, BA1, BS3, BP4P11RETG691S (Heterozygote)PP2, BA1, BS3, BP4KITA431E (Heterozygote)PM1, PM2, BP4P12RETG691S (Heterozygote)PP2, BA1, BS3, BP4RETA1051V (Heterozygote)PM1, PP2, PP3P13KITM541L (Heterozygote)PM2, BP4, BP6SDHDG12S (Heterozygote)PP2, BS1, BS3, BP4, BP6

Citation Format: Ozge Sonmezler, Isa B. Guney, Cem Mujde, Atil Bisgin. The emerging clinical relevance of genomic profiling medicine in neuroendocrine tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4154.