Standard
No difference in penetrance between truncating and missense/aberrant splicing pathogenic variants in mlh1 and msh2 : A prospective lynch syndrome database study. / Dominguez-Valentin, Mev; Plazzer, John Paul; Sampson, Julian R.; Engel, Christoph; Aretz, Stefan; Jenkins, Mark A.; Sunde, Lone; Bernstein, Inge; Capella, Gabriel; Balaguer, Francesc; Macrae, Finlay; Winship, Ingrid M.; Thomas, Huw; Evans, Dafydd 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; Della Valle, Adriana; Lopez-Kostner, Francisco; Alvarez, Karin; Gluck, Nathan; Katz, Lior; Heinimann, Karl; Vaccaro, Carlos A.; Nakken, Sigve; Hovig, Eivind; Green, Kate; Lalloo, Fiona; Hill, James; Vasen, Hans F.A.; Perne, Claudia; Büttner, Reinhard; Görgens, Heike; Holinski-Feder, Elke; Morak, Monika; Holzapfel, Stefanie; Hüneburg, Robert; Doeberitz, Magnus von Knebel; Loeffler, Markus; Rahner, Nils; Weitz, Jürgen; Steinke-Lange, Verena; Schmiegel, Wolff; Vangala, Deepak; Crosbie, Emma J.; Pineda, Marta; Navarro, Matilde; Brunet, Joan; Moreira, 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.; Win, Aung Ko; Buchanan, Daniel D.; Lindor, Noralane M.; Gallinger, Steven; Marchand, Loïc Le; 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.
In:
Journal of Clinical Medicine, Vol. 10, No. 13, 2856, 2021.
Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
Dominguez-Valentin, M, Plazzer, JP, Sampson, JR, Engel, C, Aretz, S, Jenkins, MA, Sunde, L, Bernstein, I, Capella, G, Balaguer, F, Macrae, F, Winship, IM, Thomas, H, Evans, DG, Burn, J, Greenblatt, M, de Vos tot Nederveen Cappel, WH, Sijmons, RH, Nielsen, M, Bertario, L, Bonanni, B, Tibiletti, MG, Cavestro, GM, Lindblom, A, Della Valle, A, Lopez-Kostner, F, Alvarez, K, Gluck, N, Katz, L, Heinimann, K, Vaccaro, CA, Nakken, S, Hovig, E, Green, K, Lalloo, F, Hill, J, Vasen, HFA, Perne, C, Büttner, R, Görgens, H, Holinski-Feder, E, Morak, M, Holzapfel, S, Hüneburg, R, Doeberitz, MVK, Loeffler, M, Rahner, N, Weitz, J, Steinke-Lange, V, Schmiegel, W, Vangala, D, Crosbie, EJ, Pineda, M, Navarro, M, Brunet, J, Moreira, L, Sánchez, A, Serra-Burriel, M, Mints, M, Kariv, R, Rosner, G, Piñero, TA, Pavicic, WH, Kalfayan, P, Ten Broeke, SW, Mecklin, JP, Pylvänäinen, K, Renkonen-Sinisalo, L, Lepistö, A, Peltomäki, P, Hopper, JL, Win, AK, Buchanan, DD, Lindor, NM, Gallinger, S, Marchand, LL, Newcomb, PA, Figueiredo, JC, Thibodeau, SN, Therkildsen, C
, Hansen, TVO, Lindberg, L, Rødland, EA, Neffa, F, Esperon, P, Tjandra, D, Möslein, G, Seppälä, TT & Møller, P 2021, '
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, vol. 10, no. 13, 2856.
https://doi.org/10.3390/jcm10132856
APA
Dominguez-Valentin, M., Plazzer, J. P., Sampson, J. R., Engel, C., Aretz, S., Jenkins, M. A., Sunde, L., Bernstein, I., Capella, G., Balaguer, F., Macrae, F., Winship, I. M., Thomas, H., Evans, D. G., Burn, J., Greenblatt, M., de Vos tot Nederveen Cappel, W. H., Sijmons, R. H., Nielsen, M., ... Møller, P. (2021).
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,
10(13), [2856].
https://doi.org/10.3390/jcm10132856
Vancouver
Dominguez-Valentin M, Plazzer JP, Sampson JR, Engel C, Aretz S, Jenkins MA et al.
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;10(13). 2856.
https://doi.org/10.3390/jcm10132856
Author
Dominguez-Valentin, Mev ; Plazzer, John Paul ; Sampson, Julian R. ; Engel, Christoph ; Aretz, Stefan ; Jenkins, Mark A. ; Sunde, Lone ; Bernstein, Inge ; Capella, Gabriel ; Balaguer, Francesc ; Macrae, Finlay ; Winship, Ingrid M. ; Thomas, Huw ; Evans, Dafydd 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 ; Della Valle, Adriana ; Lopez-Kostner, Francisco ; Alvarez, Karin ; Gluck, Nathan ; Katz, Lior ; Heinimann, Karl ; Vaccaro, Carlos A. ; Nakken, Sigve ; Hovig, Eivind ; Green, Kate ; Lalloo, Fiona ; Hill, James ; Vasen, Hans F.A. ; Perne, Claudia ; Büttner, Reinhard ; Görgens, Heike ; Holinski-Feder, Elke ; Morak, Monika ; Holzapfel, Stefanie ; Hüneburg, Robert ; Doeberitz, Magnus von Knebel ; Loeffler, Markus ; Rahner, Nils ; Weitz, Jürgen ; Steinke-Lange, Verena ; Schmiegel, Wolff ; Vangala, Deepak ; Crosbie, Emma J. ; Pineda, Marta ; Navarro, Matilde ; Brunet, Joan ; Moreira, 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. ; Win, Aung Ko ; Buchanan, Daniel D. ; Lindor, Noralane M. ; Gallinger, Steven ; Marchand, Loïc Le ; 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. In: Journal of Clinical Medicine. 2021 ; Vol. 10, No. 13.
Bibtex
@article{d47274b2e837492bbac5b0e8fa8f9668,
title = "No difference in penetrance between truncating and missense/aberrant splicing pathogenic variants in mlh1 and msh2: A prospective lynch syndrome database study",
abstract = "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.",
keywords = "Aberrant splicing, Cancer incidence, Lynch syndrome, Missense, MLH1, MSH2, Penetrance, Truncating",
author = "Mev Dominguez-Valentin and Plazzer, {John Paul} and Sampson, {Julian R.} and Christoph Engel and Stefan Aretz and Jenkins, {Mark A.} and Lone Sunde and Inge Bernstein and Gabriel Capella and Francesc Balaguer and Finlay Macrae and Winship, {Ingrid M.} and Huw Thomas and Evans, {Dafydd Gareth} and John Burn and Marc Greenblatt and {de Vos tot Nederveen Cappel}, {Wouter H.} and Sijmons, {Rolf H.} and Maartje Nielsen and Lucio Bertario and Bernardo Bonanni and Tibiletti, {Maria Grazia} and Cavestro, {Giulia Martina} and Annika Lindblom and {Della Valle}, Adriana and Francisco Lopez-Kostner and Karin Alvarez and Nathan Gluck and Lior Katz and Karl Heinimann and Vaccaro, {Carlos A.} and Sigve Nakken and Eivind Hovig and Kate Green and Fiona Lalloo and James Hill and Vasen, {Hans F.A.} and Claudia Perne and Reinhard B{\"u}ttner and Heike G{\"o}rgens and Elke Holinski-Feder and Monika Morak and Stefanie Holzapfel and Robert H{\"u}neburg and Doeberitz, {Magnus von Knebel} and Markus Loeffler and Nils Rahner and J{\"u}rgen Weitz and Verena Steinke-Lange and Wolff Schmiegel and Deepak Vangala and Crosbie, {Emma J.} and Marta Pineda and Matilde Navarro and Joan Brunet and Leticia Moreira and Ariadna S{\'a}nchez and Miquel Serra-Burriel and Miriam Mints and Revital Kariv and Guy Rosner and Pi{\~n}ero, {Tamara Alejandra} and Pavicic, {Walter Hern{\'a}n} and Pablo Kalfayan and {Ten Broeke}, {Sanne W.} and Mecklin, {Jukka Pekka} and Kirsi Pylv{\"a}n{\"a}inen and Laura Renkonen-Sinisalo and Anna Lepist{\"o} and P{\"a}ivi Peltom{\"a}ki and Hopper, {John L.} and Win, {Aung Ko} and Buchanan, {Daniel D.} and Lindor, {Noralane M.} and Steven Gallinger and Marchand, {Lo{\"i}c Le} and Newcomb, {Polly A.} and Figueiredo, {Jane C.} and Thibodeau, {Stephen N.} and Christina Therkildsen and Hansen, {Thomas V.O.} and Lars Lindberg and R{\o}dland, {Einar Andreas} and Florencia Neffa and Patricia Esperon and Douglas Tjandra and Gabriela M{\"o}slein and Sepp{\"a}l{\"a}, {Toni T.} and P{\aa}l M{\o}ller",
note = "Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2021",
doi = "10.3390/jcm10132856",
language = "English",
volume = "10",
journal = "Journal of Clinical Medicine",
issn = "2077-0383",
publisher = "M D P I AG",
number = "13",
}
RIS
TY - JOUR
T1 - No difference in penetrance between truncating and missense/aberrant splicing pathogenic variants in mlh1 and msh2
T2 - A prospective lynch syndrome database study
AU - Dominguez-Valentin, Mev
AU - Plazzer, John Paul
AU - Sampson, Julian R.
AU - Engel, Christoph
AU - Aretz, Stefan
AU - Jenkins, Mark A.
AU - Sunde, Lone
AU - Bernstein, Inge
AU - Capella, Gabriel
AU - Balaguer, Francesc
AU - Macrae, Finlay
AU - Winship, Ingrid M.
AU - Thomas, Huw
AU - Evans, Dafydd Gareth
AU - Burn, John
AU - Greenblatt, Marc
AU - de Vos tot Nederveen Cappel, Wouter H.
AU - Sijmons, Rolf H.
AU - Nielsen, Maartje
AU - Bertario, Lucio
AU - Bonanni, Bernardo
AU - Tibiletti, Maria Grazia
AU - Cavestro, Giulia Martina
AU - Lindblom, Annika
AU - Della Valle, Adriana
AU - Lopez-Kostner, Francisco
AU - Alvarez, Karin
AU - Gluck, Nathan
AU - Katz, Lior
AU - Heinimann, Karl
AU - Vaccaro, Carlos A.
AU - Nakken, Sigve
AU - Hovig, Eivind
AU - Green, Kate
AU - Lalloo, Fiona
AU - Hill, James
AU - Vasen, Hans F.A.
AU - Perne, Claudia
AU - Büttner, Reinhard
AU - Görgens, Heike
AU - Holinski-Feder, Elke
AU - Morak, Monika
AU - Holzapfel, Stefanie
AU - Hüneburg, Robert
AU - Doeberitz, Magnus von Knebel
AU - Loeffler, Markus
AU - Rahner, Nils
AU - Weitz, Jürgen
AU - Steinke-Lange, Verena
AU - Schmiegel, Wolff
AU - Vangala, Deepak
AU - Crosbie, Emma J.
AU - Pineda, Marta
AU - Navarro, Matilde
AU - Brunet, Joan
AU - Moreira, Leticia
AU - Sánchez, Ariadna
AU - Serra-Burriel, Miquel
AU - Mints, Miriam
AU - Kariv, Revital
AU - Rosner, Guy
AU - Piñero, Tamara Alejandra
AU - Pavicic, Walter Hernán
AU - Kalfayan, Pablo
AU - Ten Broeke, Sanne W.
AU - Mecklin, Jukka Pekka
AU - Pylvänäinen, Kirsi
AU - Renkonen-Sinisalo, Laura
AU - Lepistö, Anna
AU - Peltomäki, Päivi
AU - Hopper, John L.
AU - Win, Aung Ko
AU - Buchanan, Daniel D.
AU - Lindor, Noralane M.
AU - Gallinger, Steven
AU - Marchand, Loïc Le
AU - Newcomb, Polly A.
AU - Figueiredo, Jane C.
AU - Thibodeau, Stephen N.
AU - Therkildsen, Christina
AU - Hansen, Thomas V.O.
AU - Lindberg, Lars
AU - Rødland, Einar Andreas
AU - Neffa, Florencia
AU - Esperon, Patricia
AU - Tjandra, Douglas
AU - Möslein, Gabriela
AU - Seppälä, Toni T.
AU - Møller, Pål
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - Aberrant splicing
KW - Cancer incidence
KW - Lynch syndrome
KW - Missense
KW - MLH1
KW - MSH2
KW - Penetrance
KW - Truncating
U2 - 10.3390/jcm10132856
DO - 10.3390/jcm10132856
M3 - Journal article
C2 - 34203177
AN - SCOPUS:85114073501
VL - 10
JO - Journal of Clinical Medicine
JF - Journal of Clinical Medicine
SN - 2077-0383
IS - 13
M1 - 2856
ER -