Data from: Landscape of tumor mutation load, mismatch repair deficiency, and PD-L1 expression in a large patient cohort of gastrointestinal cancers

Purpose: The efficacy of immunotherapy varies widely among different
gastrointestinal cancers. Response to immune checkpoint inhibitors is
shown to correlate with tumor mutation load (TML), mismatch repair
deficiency status (dMMR), and programmed cell death-ligand 1 (PD-L1)
expression. Herein, we attempt to quantify TML, dMMR, and PD-L1 expression
and determine their interrelationship in gastrointestinal cancers.
Experimental Design: A total of 4125 tumors from 14 different
gastrointestinal cancer sites were studied. Next-generation sequencing was
performed on genomic DNA isolated from formalin-fixed paraffin-embedded
(FFPE) tumor samples using the NextSeq platform. TML was calculated using
only somatic nonsynonymous missense mutations sequenced with a 592-gene
panel. Microsatellite instability (MSI) was assessed by validated direct
analysis of altered known MSI loci in the target regions of the sequenced
genes. PD-L1 expression was analyzed by immunohistochemistry. Results:
Right-sided colon and small bowel adenocarcinomas had the highest
prevalence of TML-high tumors (14.6% and 10.2%, respectively). Pancreatic
neuroendocrine tumors and gastrointestinal stromal tumors (GIST) had the
lowest rates of TML-high (1.3% and 0%, respectively). TML-high status was
strongly associated with MSI-H (P<0.0001). However, all TML-high
anal cancers (8.3%) were microsatellite stable (MSS). Higher PD-L1
expression was more likely to be seen in MSI compared with MSS tumors
(20.6% vs. 7.8%, P<0.0001). Conclusions: TML-high rate varied
widely among gastrointestinal cancers. Although microsatellite instability
is conceivably the main driver for TML-high status, other factors may be
involved. Future clinical trials are needed to evaluate whether the
integration of TML, MSI, and PD-L1 could better identify potential
responders to immunotherapy.