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ESMO 2020

ESMO VIrtual Congress 2020: Co-Occurrence of Actionable Gene Fusions and Microsatellite Instability-High in 20296 Solid Tumors: A Pan-Cancer Analysis

(UroToday.com) In this study, the authors present a retrospective analysis of the co-occurrence between actionable gene mutations and microsatellite instability-high status from next-generation sequencing of 20,296 tumors collected by 3D Medicines, a precision medicine company in China.

The cohort is shown below. Fusions that were considered actionable include those involving ALK, RET, ROS1, FGFR1-4 and NTRK1-3 genes. 

Cohort-ALK-RET-ROS1-FGFR1-4_Figure1.png

The incidence of MSI-H status was highest in the uterine cancer subcohort (11%). No information was provided regarding how MSI status was ascertained.

MSI-Hstatus_uterinecancer_FIgure2.png

The incidence of actionable fusions is shown below, with lung cancers harboring the highest incidence of these genomic events (6.4%). ALK mutations were the most common fusion detected across all samples.

IncidenceActionableFusions_Figure3.png

The greatest differences in fusion status with microsatellite status was observed in intestinal cancers. Only 0.2% (9/4507) of microsatellite stable intestinal cancers had actionable fusions, but 4.2% of MSI-H (16/384)patients harbored actionable fusions, predominantly in NTRK.

Fusion_MSI-H_Figure4.png

Cases with both MSI-H and actionable fusions were profiled for mRNA expression of immune-related genes, with a suggestion of higher expression levels of TMEM173 as well as multiple MHC II genes.

Higherimmune-related_Figure5.png

These results provide additional information regarding the incidence of high levels of microsatellite instability and certain genomic fusions across a variety of cancer subtypes, and identify specific rates of co-occurrence between fusions and MSI-H. These cases show up-regulation of certain immune-related genes even relative to MSI-H tumors lacking the fusions, with potential consequences for response to immunotherapy.

Presented by: Tao Fu, Peking University Cancer Hospital, Beijing, China

Written by: Alok Tewari, MD, PhD, Medical Oncologist at the Dana-Farber Cancer Institute, at the 2020 European Society for Medical Oncology Virtual Congress (#ESMO20), September 19th-September 21st, 2020.