Tumor-infiltrating lymphocytes, tumor mutational burden, and genetic alterations in microsatellite unstable, microsatellite stable, or mutant POLE/POLD1 colon cancer Journal Article


Authors: Keshinro, A.; Vanderbilt, C.; Kim, J. K.; Firat, C.; Chen, C. T.; Yaeger, R.; Ganesh, K.; Segal, N. H.; Gonen, M.; Shia, J.; Stadler, Z.; Weiser, M. R.
Article Title: Tumor-infiltrating lymphocytes, tumor mutational burden, and genetic alterations in microsatellite unstable, microsatellite stable, or mutant POLE/POLD1 colon cancer
Abstract: PURPOSE To characterize the relationship between tumor-infiltrating lymphocytes (TIL), tumor mutational burden (TMB), and genetic alterations in microsatellite stable (MSS), microsatellite instability (MSI), or mutant POLE/POLD1 colon cancer. MATERIALS AND METHODS Four hundred ninety-nine resected stage I-III colon tumors treated between 2014 and 2019 were assessed for TIL; somatic mutations, copy number alterations, and structural changes in . 400 oncogenes; and MSI status. RESULTS Of the 499 tumors analyzed, 313 were MSS, 175 were MSI, and 11 had POLE/POLD1 pathogenic mutations. Both the percentage of tumors with a high level of TIL (≥ 4 lymphocytes per high-power field) and the median TMB differed significantly between the three phenotypes: MSS, 4.5% and 6 mutations/Mb; MSI, 68% and 54 mutations/Mb; POLE/POLD1, 82% and 158 mutations/Mb (P <.05). Within each phenotype, TMB did not vary significantly with TIL level. Among MSI tumors, the median number of frameshift indels was significantly higher in tumors with high levels of TIL (20 v 17; P = .018). In the MSS group, significantly higher proportions of tumors with high levels of TIL had mutations in the transforming growth factor-β (36% v 12%; P = .01), RAS (86% v 54%; P = .02), and Hippo (7% v 1%; P = .046) pathways; in contrast, TP53 alterations were associated with low levels of TIL (74% v 43%; P = .01). CONCLUSION The association between TIL, TMB, and genetic alterations varies significantly between MSI, MSS, and mutant POLE/POLD1 colon tumors. These differences may help explain tumoral immunity and lead to predictors of response to immunotherapy. © 2021 American Society of Clinical Oncology. All rights reserved.
Journal Title: JCO Precision Oncology
Volume: 5
ISSN: 2473-4284
Publisher: American Society of Clinical Oncology  
Date Published: 2021-01-01
Start Page: 817
End Page: 826
Language: English
DOI: 10.1200/po.20.00456
PROVIDER: scopus
PMCID: PMC8232557
PUBMED: 34250404
DOI/URL:
Notes: Article -- Export Date: 3 January 2022 -- Source: Scopus
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MSK Authors
  1. Neil Howard Segal
    210 Segal
  2. Mithat Gonen
    1030 Gonen
  3. Zsofia Kinga Stadler
    393 Stadler
  4. Jinru Shia
    720 Shia
  5. Martin R Weiser
    539 Weiser
  6. Rona Denit Yaeger
    322 Yaeger
  7. Chin-Tung Chen
    63 Chen
  8. Karuna   Ganesh
    68 Ganesh
  9. Canan Firat
    40 Firat
  10. Jin Ki Kim
    31 Kim