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Poster session 01

121P - Spectrum of druggable gene fusions in microsatellite-unstable colorectal tumors

Date

10 Sep 2022

Session

Poster session 01

Topics

Laboratory Diagnostics;  Cancer Biology;  Translational Research;  Tumour Immunology;  Pathology/Molecular Biology;  Molecular Oncology

Tumour Site

Colon and Rectal Cancer

Presenters

Evgeny Imyanitov

Citation

Annals of Oncology (2022) 33 (suppl_7): S27-S54. 10.1016/annonc/annonc1037

Authors

E. Imyanitov, A. Anuskina, A.G. Iyevleva, N.V. Mitiushkina, R. Mulkidzhan, E. Preobrazhenskaya, A. Romanko, E. Saitova, V. Tiurin

Author affiliations

  • Department Of Tumor Growth Biology, N.N. Petrov Institute of Oncology, 197758 - Saint-Petersburg/RU
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Abstract 121P

Background

Colorectal carcinomas (CRCs) with high-level microsatellite instability (MSI-H) often contain gene fusions, which involve receptor tyrosine kinases.

Methods

This study included 105 MSI-H CRCs. NTRK1/2/3, ALK, ROS1 and RET gene fusions were analyzed by PCR test for 5’/3’-end unbalanced expression, which is capable of detecting all translocation variants. The type of rearrangements was subsequently determined by variant-specific PCR for common fusions, and, wherever necessary, by targeted RNA next-generation sequencing (NGS).

Results

NTRK1/2/3 translocations were the most common, being detected in 8/105 (8%) CRCs (TPM3-NTRK1 (T8;N10): n = 2; ETV6-NTRK2 (E5;N15): n = 2; ETV6-NTRK3 (E5;N15): n = 4). There were 2 tumors with RET rearrangements (CCDC6-RET (C1;R12) and NCOA4-RET (N9del501;R12), respectively) and 1 instance of SPTBN1-ALK (S7;A20) chimera. 76/105 (72%) CRCs were negative for KRAS, NRAS or BRAF mutations; gene rearrangements were detected in 10 (13%) of these tumors. 29/105 (28%) carcinomas carried activating lesions in RAS/RAF oncogenes; one of these CRCs had both ETV6-NTRK3 (E5;N15) translocation and BRAF V600E substitution.

Conclusions

Microsatellite-unstable CRCs have high frequency of druggable gene rearrangements, with NTRK1/2/3 deserving particular attention.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Russian Science Foundation (grant 20-75-10163).

Disclosure

All authors have declared no conflicts of interest.

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