Abstract
In Lynch-like syndrome, patients have tumors with microsatellite instability but no germline pathogenic variant in mismatch repair genes or somatic methylation of the MLH1 promoter. Identification of the mechanism that causes these tumors is crucial for guiding screening of the patients and their relatives. Double somatic hits are the usual explanation for these cases; however, we have previously reported a de novo mosaic pathogenic variant in a patient with Lynch-like syndrome. Using tumoral NGS analysis of a series of 16 patients with Lynch-like syndrome, we found six patients with double somatic hits, including one patient with mosaicism of a de novo pathogenic variant in MSH2. This variant was transmitted to the patient’s offspring, which has significant implications for genetic counseling.
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Acknowledgements
The authors wish to thank the Tumorothèque des Hôpitaux Universitaires de l’Est Parisien (HUEP), AP-HP, Hôpital Tenon, the Service d’Anatomie Pathologique, F-75970 Paris, France, and the Centre de Ressources Biologiques du service d’Anatomie et Cytologie Pathologiques de la Pitié-Salpêtrière, AP-HP, F-75013 Paris, France, for providing the frozen tumor samples.
Funding
This work was supported by Assistance Publique-Hôpitaux de Paris and by grants from the Institut National du Cancer (INCa).
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Guillerm, E., Svrcek, M., Bardier-Dupas, A. et al. Molecular tumor testing in patients with Lynch-like syndrome reveals a de novo mosaic variant of a mismatch repair gene transmitted to offspring. Eur J Hum Genet 28, 1624–1628 (2020). https://doi.org/10.1038/s41431-020-0689-6
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DOI: https://doi.org/10.1038/s41431-020-0689-6
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