Microsatellite Instability Is Insufficiently Used as a Biomarker for Lynch Syndrome Testing in Clinical Practice.
In: JCO precision oncology, Jg. 8 (2024), S. e2300332
academicJournal
Zugriff:
Purpose: The pan-cancer presence of microsatellite instability (MSI)-positive tumors demonstrates its clinical utility as an agnostic biomarker for identifying immunotherapy-eligible patients. Additionally, MSI is a hallmark of Lynch syndrome (LS), the most prevalent cancer susceptibility syndrome among patients with colorectal and endometrial cancer. Therefore, MSI-high results should inform germline genetic testing for cancer-predisposing genes. However, in clinical practice, such analysis is frequently disregarded.
Methods: A next-generation sequencing (NGS)-based technique was used for MSI analysis in 4,553 patients with various tumor types. Upon request, somatic BRAF gene analysis was conducted. In addition, hereditary testing of cancer-associated genes was performed in MSI-high cases using a capture-based NGS protocol. MLH1 promoter methylation analysis was conducted retrospectively in patients with colorectal and endometrial cancer to further investigate the origin of MSI at the tumor level.
Results: The MSI positivity rate for the entire cohort was 5.27%. Endometrial, gastric, colorectal, urinary tract, and prostate cancers showed the highest proportion of MSI-high cases (15.69%, 8.54%, 7.40%, 4.55%, and 3.19%, respectively). A minority of 45 patients (22.73%) among the MSI-high cases underwent germline testing to determine whether the mismatch repair pathway deficiency was inherited. 24.44% of those who performed the genetic test carried a pathogenic variant in an LS-associated gene. Three MSI-high individuals had non-LS gene alterations, including BRCA1 , BRCA2 , and CDKN2A pathogenic variants, indicating the presence of non-LS-associated gene alterations among MSI-high patients.
Conclusion: Although MSI analysis is routinely performed in clinical practice, as many as 77% of MSI-high patients do not undergo LS genetic testing, despite international guidelines strongly recommending it. BRAF and MLH1 methylation analysis could shed light on the somatic origin of MSI in 42.50% of the MSI-high patients; however, MLH1 analysis is barely ever requested in clinical practice.
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Microsatellite Instability Is Insufficiently Used as a Biomarker for Lynch Syndrome Testing in Clinical Practice.
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Autor/in / Beteiligte Person: | Papadopoulou, E ; Rigas, G ; Fountzilas, E ; Boutis, A ; Giassas, S ; Mitsimponas, N ; Daliani, D ; Ziogas, DC ; Liontos, M ; Ramfidis, V ; Christophilakis, C ; Matthaios, D ; Floros, T ; Florou-Chatzigiannidou, C ; Agiannitopoulos, K ; Meintani, A ; Tsantikidi, A ; Katseli, A ; Potska, K ; Tsaousis, G ; Metaxa-Mariatou, V ; Nasioulas, G |
Zeitschrift: | JCO precision oncology, Jg. 8 (2024), S. e2300332 |
Veröffentlichung: | Alexandria, VA : American Society of Clinical Oncology, [2017]-, 2024 |
Medientyp: | academicJournal |
ISSN: | 2473-4284 (electronic) |
DOI: | 10.1200/PO.23.00332 |
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