Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

5934 - Microsatellite instability-high (MSI-H) colorectal cancers with elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) signature represent a target population for immune checkpoint and DNA damaging therapies

Date

20 Oct 2018

Session

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Topics

Targeted Therapy;  Colon and Rectal Cancer

Presenters

Kien Thiam Tan

Citation

Annals of Oncology (2018) 29 (suppl_8): viii14-viii57. 10.1093/annonc/mdy269

Authors

K.T. Tan1, P. Yu2, S. Chen2, Y. Liu2, S. Chang3, M. Chen4

Author affiliations

  • 1 Medical Informatics, ACT Genomics, Co., LTD, 114 - Taipei/TW
  • 2 Medical Informatics, ACT Genomics Co., Ltd., Taipei/TW
  • 3 Department Of Surgery, Faculty Of Medicine,, National Yang-Ming University, 112 - Taipei/TW
  • 4 Department Of Oncology, Taipei Veterans General Hospital, 11211 - Taipei/TW
More

Resources

Abstract 5934

Background

Elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) is a different type of genomic instability in colon cancer (CRC) in contrast to mono-, and dinucleotide based instability microsatellite instability (MSI). In this study, we performed comprehensive genomic profiling (CGP) of CRC patients with different EMAST and MSI status to understand their genomic structure, which may help match them with relevant therapies.

Methods

99 formalin-fixed, paraffin-embedded (FFPE) CRC tissues consisting of four subtypes based on their EMAST and MSI status, namely (1) EMAST+ and MSI-high (MSI-H), (2) EMAST+ and microsatellite‐stable (MSS), (3) EMAST- and MSI-H, and (4) EMATS- and MSS, were subjected to next-generation sequencing (NGS) with a 440-gene panel to identify mutations and copy number variants (CNVs). Tumor mutational burden (TMB) was determined using mutations detected on exonic regions sequenced while CNV index was calculated to infer genome instability.

Results

In line with previous studies, the prevalence of TP53 (17.6%; n = 3) and APC (23.5%; n = 4) mutations was much lower whereas BRAF V600 mutation (41.2%; n = 7) was much higher in the subtype (1) CRCs which had both MSI-H and EMAST signatures. Interestingly, these dual positive tumors had a significant higher TMB and lower CNV index than other subtypes (TMB: (1) vs (2), (3) and (4); 54 vs 19, 25; and 16; p < 0.0001, CNV index: (1) vs (2), (3), and (4); 3.9 vs 13.7, 9.9, and 17.8; p < 0.0114, 0.006, and 0.0003), suggesting there are more likely to benefit from immune checkpoint inhibitors. Notably, ATM and ARID1A genes mutated in a mutually exclusive way in up to 13/17 (76.5%) of tumors with MSI-H and EMAST signatures, which may predict treatment benefit from the PARP inhibitors.

Conclusions

MSI-H and EMAST+ CRCs show distinctive genomic features that give them the potential opportunity for checkpoint inhibitors in combination with PARP inhibitors.

Clinical trial identification

Legal entity responsible for the study

ACT Genomics.

Funding

Has not received any funding.

Editorial Acknowledgement

Disclosure

K.T. Tan, S-J. Chen: Shareholder: ACT Genomics. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.