Low microsatellite instability: a distinct instability type in gastric cancer?
Purpose We recently showed that low microsatellite instability (MSI-L) is associated with a good response to platinum/5fluorouracil (5-FU) neoadjuvant chemotherapy (CTx) in gastric cancer. The purpose of this study was to characterize the instability pattern and to investigate an association of MSI...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
11 October 2023
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| In: |
Journal of cancer research and clinical oncology
Year: 2023, Volume: 149, Issue: 20, Pages: 17727-17737 |
| ISSN: | 1432-1335 |
| DOI: | 10.1007/s00432-023-05430-6 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1007/s00432-023-05430-6 Verlag, kostenfrei, Volltext: https://link.springer.com/10.1007/s00432-023-05430-6 
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| Author Notes: | Meike Kohlruss, Shounak Chakraborty, Alexander Hapfelmeier, Moritz Jesinghaus, Julia Slotta-Huspenina, Alexander Novotny, Leila Sisic, Matthias M. Gaida, Katja Ott, Wilko Weichert, Nicole Pfarr, Gisela Keller |
| Summary: | Purpose We recently showed that low microsatellite instability (MSI-L) is associated with a good response to platinum/5fluorouracil (5-FU) neoadjuvant chemotherapy (CTx) in gastric cancer. The purpose of this study was to characterize the instability pattern and to investigate an association of MSI-L tumors with mutations in genes of DNA repair pathways and with total tumor mutation burden (TMB). - Methods MSI patterns were compared between 67 MSI high (-H) and 35 MSI-L tumors. Whole-exome sequencing was performed in 34 microsatellite stable (MSS) and 20 MSI-L tumors after or without neoadjuvant CTx. - Results Of the 35 MSI-L tumors, 33 tumors had instability at a dinucleotide repeat marker. In the homologous recombination (HR) pathway, 10 of the 34 (29%) MSS and 10 of the 20 (50%) MSI-L tumors showed variants (p = 0.154). In the DNA damage tolerance pathway, 6 of the 34 (18%) MSS and 7 of the 20 (35%) MSI-L tumors had variants (p = 0.194). The HR deficiency score was similar in both tumor groups. TMB was significantly higher in MSI-L compared to MSS tumors after CTx (p = 0.046). In the MSS and MSI-L tumors without CTx no difference was observed (p = 1.00). - Conclusion MSI-L due to instability at dinucleotide repeat markers was associated with increased TMB after neoadjuvant CTx treatment, indicating sensitivity to platinum/5-FU CTx. If confirmed in further studies, this could contribute to refined chemotherapeutic options including immune-based strategies for GC patients with MSI-L tumors. |
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| Item Description: | Gesehen am 18.12.2023 |
| Physical Description: | Online Resource |
| ISSN: | 1432-1335 |
| DOI: | 10.1007/s00432-023-05430-6 |