Targeted gene sequencing panels: applicability for neoantigen profiling of colon and rectal adenocarcinoma

   
Kanygina A.V.1 , Sharova E.I.1, Sultanov R.I.1, Schelygin Y.A.2, Doludin Y.V.3, Kostryukova E.S.1, Generozov E.V.1

1. Federal Research and Clinical Center of Physical-Chemical Medicine, Moscow, Russia
2. State Scientific Center of Coloproctology, Moscow, Russia
3. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
Section: Clinical and Diagnostic Research
DOI: 10.18097/PBMC20186406517      PubMed Id: 30632980
Year: 2018  Volume: 64  Issue: 6  Pages: 517-524
Cancer immunotherapy represents a promising and rapidly developing approach for the treatment of oncological diseases. Among the methods of personalized adjuvant immunotherapy, neoantigenic peptide-based drugs have demonstrated substantial efficiency. These drugs are designed to target mutant proteins arising from somatic alterations in the genome of tumor cells and thus stimulate immune response against tumor tissues. The methods of individual screening for potentially immunogenic mutations are mostly based on next-generation exome sequencing of tumor samples, which is a complex and costly procedure for clinical application. Targeted gene sequencing panels limited to a certain set of genes represent a reasonable alternative to WES. Targeted sequencing is also more efficient when there is a low amount of the sample DNA available. We have estimated the potential efficiency of targeted oncological panels in terms of somatic neoantigen profiling in colorectal cancer (colon and rectal adenocarcinoma). The clinical practice of identification of frequent somatic variants does not provide enough data for designing an efficient personalized drug when applied to low and medium mutated cancers such as colorectal cancer. Our analysis of 11 commercially available panels containing different number of genes has shown that neither the larger size of a panel nor its initial customization for colorectal cancer provides a significantly better estimation of an individual somatic mutation profile. The optimal approach is to use the general-purpose medium-sized cancer panels (2300-11200 amplicons and/or 150-600 genes). These panels allow to detect a sufficient number of immunogenic epitopes (>3) per patient for over 30-50% of patients.
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Keywords: colorectal cancer, neoantigens, immunotherapy, sequencing, targeted panels
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Citation:

Kanygina, A. V., Sharova, E. I., Sultanov, R. I., Schelygin, Y. A., Doludin, Y. V., Kostryukova, E. S., Generozov, E. V. (2018). Targeted gene sequencing panels: applicability for neoantigen profiling of colon and rectal adenocarcinoma. Biomeditsinskaya Khimiya, 64(6), 517-524.
This paper is also available as the English translation: 10.1134/S1990750819020045
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