Three molecular pathways model colorectal carcinogenesis in Lynch syndrome
Lynch syndrome is caused by germline mutations of DNA mismatch repair (MMR) genes. MMR deficiency has long been regarded as a secondary event in the pathogenesis of Lynch syndrome colorectal cancers. Recently, this concept has been challenged by the discovery of MMR-deficient crypt foci in the norma...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
9 Feb 2018
|
| In: |
Molecular cancer research
Year: 2018, Volume: 143, Issue: 1, Pages: 139-150 |
| ISSN: | 1557-3125 |
| DOI: | 10.1002/ijc.31300 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1002/ijc.31300 Verlag, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.31300 
|
| Author Notes: | Aysel Ahadova, Richard Gallon, Johannes Gebert, Alexej Ballhausen, Volker Endris, Martina Kirchner, Albrecht Stenzinger, John Burn, Magnus von Knebel Doeberitz, Hendrik Bläker and Matthias Kloor |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1663607192 | ||
| 003 | DE-627 | ||
| 005 | 20220816141646.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 190425s2018 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1002/ijc.31300 |2 doi | |
| 035 | |a (DE-627)1663607192 | ||
| 035 | |a (DE-599)KXP1663607192 | ||
| 035 | |a (OCoLC)1341211803 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Ahadova, Aysel |d 1988- |e VerfasserIn |0 (DE-588)106835268X |0 (DE-627)820167118 |0 (DE-576)427724783 |4 aut | |
| 245 | 1 | 0 | |a Three molecular pathways model colorectal carcinogenesis in Lynch syndrome |c Aysel Ahadova, Richard Gallon, Johannes Gebert, Alexej Ballhausen, Volker Endris, Martina Kirchner, Albrecht Stenzinger, John Burn, Magnus von Knebel Doeberitz, Hendrik Bläker and Matthias Kloor |
| 264 | 1 | |c 9 Feb 2018 | |
| 300 | |a 13 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 25.04.2019 | ||
| 520 | |a Lynch syndrome is caused by germline mutations of DNA mismatch repair (MMR) genes. MMR deficiency has long been regarded as a secondary event in the pathogenesis of Lynch syndrome colorectal cancers. Recently, this concept has been challenged by the discovery of MMR-deficient crypt foci in the normal mucosa. We aimed to reconstruct colorectal carcinogenesis in Lynch syndrome by collecting molecular and histology evidence from Lynch syndrome adenomas and carcinomas. We determined the frequency of MMR deficiency in adenomas from Lynch syndrome mutation carriers by immunohistochemistry and by systematic literature analysis. To trace back the pathways of pathogenesis, histological growth patterns and mutational signatures were analyzed in Lynch syndrome colorectal cancers. Literature and immunohistochemistry analysis demonstrated MMR deficiency in 491 (76.7%) out of 640 adenomas (95% CI: 73.3% to 79.8%) from Lynch syndrome mutation carriers. Histologically normal MMR-deficient crypts were found directly adjacent to dysplastic adenoma tissue, proving their role as tumor precursors in Lynch syndrome. Accordingly, mutation signature analysis in Lynch colorectal cancers revealed that KRAS and APC mutations commonly occur after the onset of MMR deficiency. Tumors lacking evidence of polypous growth frequently presented with CTNNB1 and TP53 mutations. Our findings demonstrate that Lynch syndrome colorectal cancers can develop through three pathways, with MMR deficiency commonly representing an early and possibly initiating event. This underlines that targeting MMR-deficient cells by chemoprevention or vaccines against MMR deficiency-induced frameshift peptide neoantigens holds promise for tumor prevention in Lynch syndrome. | ||
| 650 | 4 | |a colorectal cancer | |
| 650 | 4 | |a Lynch syndrome | |
| 650 | 4 | |a microsatellite instability | |
| 650 | 4 | |a mismatch repair deficiency | |
| 700 | 1 | |a Gebert, Johannes |e VerfasserIn |0 (DE-588)1033923567 |0 (DE-627)743674731 |0 (DE-576)381600688 |4 aut | |
| 700 | 1 | |a Endris, Volker |e VerfasserIn |0 (DE-588)1063753686 |0 (DE-627)812590961 |0 (DE-576)422898198 |4 aut | |
| 700 | 1 | |a Kirchner, Martina |d 1973- |e VerfasserIn |0 (DE-588)1017178976 |0 (DE-627)676266363 |0 (DE-576)353239747 |4 aut | |
| 700 | 1 | |a Stenzinger, Albrecht |e VerfasserIn |0 (DE-588)139606106 |0 (DE-627)703395238 |0 (DE-576)312432755 |4 aut | |
| 700 | 1 | |a Knebel Doeberitz, Magnus von |e VerfasserIn |0 (DE-588)1022165291 |0 (DE-627)71693289X |0 (DE-576)364934239 |4 aut | |
| 700 | 1 | |a Kloor, Matthias |d 1972- |e VerfasserIn |0 (DE-588)124552803 |0 (DE-627)363416609 |0 (DE-576)294228616 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Molecular cancer research |d Philadelphia, Pa. : AACR, 2002 |g 143(2018), 1, Seite 139-150 |h Online-Ressource |w (DE-627)359783538 |w (DE-600)2097884-4 |w (DE-576)105430749 |x 1557-3125 |7 nnas |a Three molecular pathways model colorectal carcinogenesis in Lynch syndrome |
| 773 | 1 | 8 | |g volume:143 |g year:2018 |g number:1 |g pages:139-150 |g extent:13 |a Three molecular pathways model colorectal carcinogenesis in Lynch syndrome |
| 856 | 4 | 0 | |u https://doi.org/10.1002/ijc.31300 |x Verlag |x Resolving-System |3 Volltext |
| 856 | 4 | 0 | |u https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.31300 |x Verlag |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20190425 | ||
| 993 | |a Article | ||
| 994 | |a 2018 | ||
| 998 | |g 124552803 |a Kloor, Matthias |m 124552803:Kloor, Matthias |d 910000 |d 912000 |e 910000PK124552803 |e 912000PK124552803 |k 0/910000/ |k 1/910000/912000/ |p 11 |y j | ||
| 998 | |g 1022165291 |a Knebel Doeberitz, Magnus von |m 1022165291:Knebel Doeberitz, Magnus von |d 910000 |d 912000 |e 910000PK1022165291 |e 912000PK1022165291 |k 0/910000/ |k 1/910000/912000/ |p 9 | ||
| 998 | |g 139606106 |a Stenzinger, Albrecht |m 139606106:Stenzinger, Albrecht |d 910000 |d 912000 |e 910000PS139606106 |e 912000PS139606106 |k 0/910000/ |k 1/910000/912000/ |p 7 | ||
| 998 | |g 1017178976 |a Kirchner, Martina |m 1017178976:Kirchner, Martina |d 50000 |e 50000PK1017178976 |k 0/50000/ |p 6 | ||
| 998 | |g 1063753686 |a Endris, Volker |m 1063753686:Endris, Volker |d 910000 |d 912000 |e 910000PE1063753686 |e 912000PE1063753686 |k 0/910000/ |k 1/910000/912000/ |p 5 | ||
| 998 | |g 1033923567 |a Gebert, Johannes |m 1033923567:Gebert, Johannes |d 910000 |d 912000 |e 910000PG1033923567 |e 912000PG1033923567 |k 0/910000/ |k 1/910000/912000/ |p 3 | ||
| 998 | |g 106835268X |a Ahadova, Aysel |m 106835268X:Ahadova, Aysel |d 910000 |d 912000 |e 910000PA106835268X |e 912000PA106835268X |k 0/910000/ |k 1/910000/912000/ |p 1 |x j | ||
| 999 | |a KXP-PPN1663607192 |e 3453366980 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"note":["Gesehen am 25.04.2019"],"title":[{"title_sort":"Three molecular pathways model colorectal carcinogenesis in Lynch syndrome","title":"Three molecular pathways model colorectal carcinogenesis in Lynch syndrome"}],"id":{"doi":["10.1002/ijc.31300"],"eki":["1663607192"]},"recId":"1663607192","relHost":[{"recId":"359783538","pubHistory":["1.2002 -"],"titleAlt":[{"title":"MCR"}],"corporate":[{"role":"isb","display":"American Association for Cancer Research","roleDisplay":"Herausgebendes Organ"}],"type":{"bibl":"periodical","media":"Online-Ressource"},"origin":[{"publisherPlace":"Philadelphia, Pa.","dateIssuedKey":"2002","dateIssuedDisp":"2002-","publisher":"AACR"}],"language":["eng"],"name":{"displayForm":["American Association for Cancer Research"]},"physDesc":[{"extent":"Online-Ressource"}],"part":{"issue":"1","volume":"143","text":"143(2018), 1, Seite 139-150","pages":"139-150","extent":"13","year":"2018"},"id":{"issn":["1557-3125"],"eki":["359783538"],"zdb":["2097884-4"]},"title":[{"subtitle":"MCR","title_sort":"Molecular cancer research","title":"Molecular cancer research"}],"note":["Gesehen am 08.06.2023","Fortsetzung der Druck-Ausgabe"],"disp":"Three molecular pathways model colorectal carcinogenesis in Lynch syndromeMolecular cancer research"}],"name":{"displayForm":["Aysel Ahadova, Richard Gallon, Johannes Gebert, Alexej Ballhausen, Volker Endris, Martina Kirchner, Albrecht Stenzinger, John Burn, Magnus von Knebel Doeberitz, Hendrik Bläker and Matthias Kloor"]},"person":[{"role":"aut","display":"Ahadova, Aysel","given":"Aysel","roleDisplay":"VerfasserIn","family":"Ahadova"},{"family":"Gebert","roleDisplay":"VerfasserIn","given":"Johannes","role":"aut","display":"Gebert, Johannes"},{"display":"Endris, Volker","role":"aut","given":"Volker","roleDisplay":"VerfasserIn","family":"Endris"},{"family":"Kirchner","roleDisplay":"VerfasserIn","given":"Martina","display":"Kirchner, Martina","role":"aut"},{"family":"Stenzinger","roleDisplay":"VerfasserIn","given":"Albrecht","role":"aut","display":"Stenzinger, Albrecht"},{"role":"aut","display":"Knebel Doeberitz, Magnus von","given":"Magnus von","family":"Knebel Doeberitz","roleDisplay":"VerfasserIn"},{"given":"Matthias","role":"aut","display":"Kloor, Matthias","family":"Kloor","roleDisplay":"VerfasserIn"}],"physDesc":[{"extent":"13 S."}],"language":["eng"],"type":{"media":"Online-Ressource","bibl":"article-journal"},"origin":[{"dateIssuedKey":"2018","dateIssuedDisp":"9 Feb 2018"}]} | ||
| SRT | |a AHADOVAAYSTHREEMOLEC9201 | ||