83MO - Co-occurrence of actionable gene fusions and microsatellite instability-high (MSI-H) in 20296 solid tumors: A pan-cancer analysis

Background

In solid tumors, both actionable gene fusions and MSI-H were rare but associated with better prognosis due to the promising treatments of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). Limited by the low incidence rates of fusions and MSI-H, the association between these two biomarkers remains largely unknown. Here we aimed at characterizing the distribution of fusions and MSI-H in 20296 solid tumors.

Methods

Hybrid capture-based next-generation sequencing (NGS) were performed in 20296 samples of solid tumors and matched normal pairs in a CAP/CLIA-approved laboratory (3DMed). NGS testing for germline and somatic mutations, copy number variation, fusion, and MSI were implemented.

Results

Of the 20296 tumor samples, MSI-H and fusion of ALK/RET/ROS1/FGFR/NTRK were observed in 620 (3.05%) and 410 samples (2.02%), respectively. MSI-H was relatively more prevalent in tumors of uterus (11.03%), intestine (7.85%), and stomach (4.98%), while 78.5% of fusion events were observed in lung cancers. In total, the incidence rate of fusion was higher in the MSI-H samples, compared to the MSS samples (3.06% vs. 1.99%, OR=1.56, P=0.079). This positive correlation was remarkably significant in cancers of intestine (OR=21.73, P=1.64*10^-12), where merely 9 fusions (6 of RET, 2 of NTRK, and 1 of ALK) were observed in 4507 MSS samples (0.20%), while 16 fusions (4 of RET, 8 of NTRK, and 4 of ALK) were detected in 384 MSI-H samples (7.85%). Table: 83MO

Association between gene fusion and MSI-H in the 20296 solid tumors

Conclusions

Our results revealed the positive correlation between actionable gene fusion and MSI-H in solid tumors, especially cancers of intestine. In the rare patients with both actionable gene fusion and MSI-H, observation and comparison of the anti-tumor activities of TKI and ICI are warranted.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Peking University Cancer Hospital.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.