In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e16699-e16699
Abstract:
e16699 Background: Pancreatic neuroendocrine tumors (panNETs) are a heterogeneous, relatively rare type of neoplasm which distinguishes a long clinical course in a large number of cases, that leads to the fact that the prevalence rate of NETs is one of the highest. The purpose of this study was a research the mutational profiles of panNETs of various grades of malignancy and to search for new candidate genes involved in the oncogenic processes of this pathology. Methods: The study included a retrospective group of 24 patients (10 men, 14 women, median age - 60 years old) with a diagnosis of panNET, treated in the RRIO from 2011 to 2018. Comprehensive cancer panel (409 genes) were used for NGS procedure on the NextSeq 550 platform(Illumina, USA). To work with raw data, we used the standard pipeline proposed by BaseSpace (Illumina, USA). Interpretation of the identified variants was carried out in accordance with the recommendations of the Association for Molecular Pathology, American Society of Clinical Oncology and College of American Pathologists. Results: 119 mutations in 54 genes were detected in samples of panNETs. 26 genetic variations were characterized as new, not previously described for panNETs. 18% of the mutations were activating, 35% of the variants led to a loss of function of the encoded protein, 52% were not classified. Candidate genes that have not been previously described in the literature and which are potentially involved in pancreatic oncogenesis are identified: CREB1, TCF12, PRKAR1A, BCL11A and BUB1B. The largest number of mutational events occurred in the genes responsible for histone methylation; in addition, 38% described genetic alterations in the regulation of the SMAD2/3 signaling pathway. Conclusions: According to the NGS study of panNETs of low and moderate malignancy in the Russian cohort, a unique spectrum of 119 mutations was obtained, of which 26 were not previously described. The discovered molecular genetic changes in the signaling pathways underline the importance of impaired epigenetic control of transcription in pancreatic oncogenesis and open up new prospects for targeted therapy.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2020.38.15_suppl.e16699
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2020
detail.hit.zdb_id:
2005181-5
