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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/179425
No Difference in Penetrance between Truncating and Missense/Aberrant Splicing Pathogenic Variants in MLH1 and MSH2: A Prospective Lynch Syndrome Database Study
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Background: Lynch syndrome is the most common genetic predisposition for hereditary cancer. Carriers of pathogenic changes in mismatch repair (MMR) genes have an increased risk of developing colorectal (CRC), endometrial, ovarian, urinary tract, prostate, and other cancers, depending on which gene is malfunctioning. In Lynch syndrome, differences in cancer incidence (penetrance) according to the gene involved have led to the stratification of cancer surveillance. By contrast, any differences in penetrance determined by the type of pathogenic variant remain unknown. Objective: To determine cumulative incidences of cancer in carriers of truncating and missense or aberrant splicing pathogenic variants of the MLH1 and MSH2 genes. Methods: Carriers of pathogenic variants of MLH1 (path_MLH1) and MSH2 (path_MSH2) genes filed in the Prospective Lynch Syndrome Database (PLSD) were categorized as truncating or missense/aberrant splicing according to the InSiGHT criteria for pathogenicity. Results: Among 5199 carriers, 1045 had missense or aberrant splicing variants, and 3930 had truncating variants. Prospective observation years for the two groups were 8205 and 34,141 years, respectively, after which there were no significant differences in incidences for cancer overall or for colorectal cancer or endometrial cancers separately. Conclusion: Truncating and missense or aberrant splicing pathogenic variants were associated with similar average cumulative incidences of cancer in carriers of path MLH1 and path_MSH2.
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DOMINGUEZ VALENTIN, Mev, PLAZZER, John-paul, SAMPSON, Julian r., ENGEL, Christoph, ARETZ, Stefan, JENKINS, Mark a., SUNDE, Lone, BERNSTEIN, Inge, CAPELLÁ, G. (gabriel), BALAGUER PRUNÉS, Francesc, MACRAE, Finlay, WINSHIP, Ingrid m., THOMAS, Huw, EVANS, D. gareth, BURN, John, GREENBLATT, Marc, DE VOS TOT NEDERVEEN CAPPEL, Wouter h., SIJMONS, Rolf h., NIELSEN, Maartje, BERTARIO, Lucio, BONANNI, Bernardo, TIBILETTI, Maria grazia, CAVESTRO, Giulia martina, LINDBLOM, Annika, VALLE, Adriana della, LOPEZ KOSTNER, Francisco, ALVAREZ VALENZUELA, Karin, GLUCK, Nathan, KATZ, Lior, HEINIMANN, Karl, VACCARO, Carlos a., NAKKEN, Sigve, HOVIG, Eivind, GREEN, Kate, LALLOO, Fiona, HILL, James, VASEN, Hans, PERNE, Claudia, BÜTTNER, Reinhard, GÖRGENS, Heike, HOLINSKI FEDER, Elke, MORAK, Monika, HOLZAPFEL, Stefanie, HÜNEBURG, Robert, VON KNEBEL DOEBERITZ, Magnus, LOEFFLER, Markus, RAHNER, Nils, WEITZ, Jürgen, STEINKE-LANGE, Verena, SCHMIEGEL, Wolff, VANGALA, Deepak, CROSBIE, Emma j., PINEDA, Marta, NAVARRO, Matilde, BRUNET, Joan, MOREIRA RUIZ, Leticia, SÁNCHEZ, Ariadna, SERRA BURRIEL, Miquel, MINTS, Miriam, KARIV, Revital, ROSNER, Guy, PIÑERO, Tamara alejandra, PAVICIC, Walter hernán, KALFAYAN, Pablo, TEN BROEKE, Sanne w., MECKLIN, Jukka-pekka, PYLVÄNÄINEN, Kirsi, RENKONEN SINISALO, Laura, LEPISTÖ, Anna, PELTOMÄKI, Päivi, HOPPER, John l., KO WIN, Aung, BUCHANAN, Daniel d., LINDOR, Noralane m., GALLINGER, Steven, LE MARCHAND, Loïc, NEWCOMB, Polly a., FIGUEIREDO, Jane c., THIBODEAU, Stephen n., THERKILDSEN, Christina, HANSEN, Thomas v. o., LINDBERG, Lars, RØDLAND, Einar andreas, NEFFA, Florencia, ESPERON, Patricia, TJANDRA, Douglas, MÖSLEIN, Gabriela, SEPPÄLÄ, Toni t., MØLLER, Pål. No Difference in Penetrance between Truncating and Missense/Aberrant Splicing Pathogenic Variants in MLH1 and MSH2: A Prospective Lynch Syndrome Database Study. _Journal of Clinical Medicine_. 2021. Vol. 10, núm. 13, pàgs. 2856. [consulta: 27 de gener de 2026]. ISSN: 2077-0383. [Disponible a: https://hdl.handle.net/2445/179425]