Mismatch repair-deficient crypt foci in Lynch syndrome: molecular alterations and association with clinical parameters
Lynch syndrome is caused by germline mutations of DNA mismatch repair (MMR) genes, most frequently MLH1 and MSH2. Recently, MMR-deficient crypt foci (MMR-DCF) have been identified as a novel lesion which occurs at high frequency in the intestinal mucosa from Lynch syndrome mutation carriers, but ver...
Gespeichert in:
| Hauptverfasser: | , , , , , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
March 27, 2015
|
| In: |
PLOS ONE
Year: 2015, Jahrgang: 10, Heft: 3, Pages: 1-15 |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0121980 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1371/journal.pone.0121980 Verlag, kostenfrei, Volltext: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0121980 Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1371/journal.pone.0121980 Verlag, kostenfrei, Volltext: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4376900/ 
|
| Verfasserangaben: | Laura Staffa, Fabian Echterdiek, Nina Nelius, Axel Benner, Wiebke Werft, Bernd Lahrmann, Niels Grabe, Martin Schneider, Mirjam Tariverdian, Magnus von Knebel Doeberitz, Hendrik Bläker, Matthias Kloor |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1562474103 | ||
| 003 | DE-627 | ||
| 005 | 20241029094447.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 170816s2015 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1371/journal.pone.0121980 |2 doi | |
| 035 | |a (DE-627)1562474103 | ||
| 035 | |a (DE-576)492474109 | ||
| 035 | |a (DE-599)BSZ492474109 | ||
| 035 | |a (OCoLC)1340978545 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Staffa, Laura |d 1988- |e VerfasserIn |0 (DE-588)1068352116 |0 (DE-627)820165972 |0 (DE-576)427723981 |4 aut | |
| 245 | 1 | 0 | |a Mismatch repair-deficient crypt foci in Lynch syndrome |b molecular alterations and association with clinical parameters |c Laura Staffa, Fabian Echterdiek, Nina Nelius, Axel Benner, Wiebke Werft, Bernd Lahrmann, Niels Grabe, Martin Schneider, Mirjam Tariverdian, Magnus von Knebel Doeberitz, Hendrik Bläker, Matthias Kloor |
| 264 | 1 | |c March 27, 2015 | |
| 300 | |b Illustrationen | ||
| 300 | |a 15 | ||
| 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 29.10.2024 | ||
| 520 | |a Lynch syndrome is caused by germline mutations of DNA mismatch repair (MMR) genes, most frequently MLH1 and MSH2. Recently, MMR-deficient crypt foci (MMR-DCF) have been identified as a novel lesion which occurs at high frequency in the intestinal mucosa from Lynch syndrome mutation carriers, but very rarely progress to cancer. To shed light on molecular alterations and clinical associations of MMR-DCF, we systematically searched the intestinal mucosa from Lynch syndrome patients for MMR-DCF by immunohistochemistry. The identified lesions were characterised for alterations in microsatellite-bearing genes with proven or suspected role in malignant transformation. We demonstrate that the prevalence of MMR-DCF (mean 0.84 MMR-DCF per 1 cm2 mucosa in the colorectum of Lynch syndrome patients) was significantly associated with patients’ age, but not with patients’ gender. No MMR-DCF were detectable in the mucosa of patients with sporadic MSI-H colorectal cancer (n = 12). Microsatellite instability of at least one tested marker was detected in 89% of the MMR-DCF examined, indicating an immediate onset of microsatellite instability after MMR gene inactivation. Coding microsatellite mutations were most frequent in the genes HT001 (ASTE1) with 33%, followed by AIM2 (17%) and BAX (10%). Though MMR deficiency alone appears to be insufficient for malignant transformation, it leads to measurable microsatellite instability even in single MMR-deficient crypts. Our data indicate for the first time that the frequency of MMR-DCF increases with patients’ age. Similar patterns of coding microsatellite instability in MMR-DCF and MMR-deficient cancers suggest that certain combinations of coding microsatellite mutations, including mutations of the HT001, AIM2 and BAX gene, may contribute to the progression of MMR-deficient lesions into MMR-deficient cancers. | ||
| 650 | 4 | |a Colorectal cancer | |
| 650 | 4 | |a Gastrointestinal cancers | |
| 650 | 4 | |a Germline mutation | |
| 650 | 4 | |a Hereditary nonpolyposis colorectal cancer | |
| 650 | 4 | |a Heredity | |
| 650 | 4 | |a Lesions | |
| 650 | 4 | |a Microsatellite loci | |
| 650 | 4 | |a Mutation | |
| 700 | 1 | |a Echterdiek, Fabian Friedrich |d 1988- |e VerfasserIn |0 (DE-588)1077930208 |0 (DE-627)837744105 |0 (DE-576)44715012X |4 aut | |
| 700 | 1 | |a Nelius, Nina |e VerfasserIn |0 (DE-588)1138292184 |0 (DE-627)895606550 |0 (DE-576)492468273 |4 aut | |
| 700 | 1 | |a Benner, Axel |d 1959- |e VerfasserIn |0 (DE-588)106584686X |0 (DE-627)81687221X |0 (DE-576)425536602 |4 aut | |
| 700 | 1 | |a Werft, Wiebke |d 1978- |e VerfasserIn |0 (DE-588)1012483967 |0 (DE-627)661826945 |0 (DE-576)345464486 |4 aut | |
| 700 | 1 | |a Lahrmann, Bernd |d 1982- |e VerfasserIn |0 (DE-588)1022879715 |0 (DE-627)717324710 |0 (DE-576)366112821 |4 aut | |
| 700 | 1 | |a Grabe, Niels |e VerfasserIn |0 (DE-588)123210615 |0 (DE-627)716920697 |0 (DE-576)364937602 |4 aut | |
| 700 | 1 | |a Schneider, Martin |d 1976- |e VerfasserIn |0 (DE-588)12390384X |0 (DE-627)706468147 |0 (DE-576)42325037X |4 aut | |
| 700 | 1 | |a Tariverdian, Mirjam |d 1947- |e VerfasserIn |0 (DE-588)131506641 |0 (DE-627)510155995 |0 (DE-576)298552000 |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 PLOS ONE |d San Francisco, California, US : PLOS, 2006 |g 10(2015), 3, Artikel-ID e0121980, Seite 1-15 |h Online-Ressource |w (DE-627)523574592 |w (DE-600)2267670-3 |w (DE-576)281331979 |x 1932-6203 |7 nnas |a Mismatch repair-deficient crypt foci in Lynch syndrome molecular alterations and association with clinical parameters |
| 773 | 1 | 8 | |g volume:10 |g year:2015 |g number:3 |g elocationid:e0121980 |g pages:1-15 |g extent:15 |a Mismatch repair-deficient crypt foci in Lynch syndrome molecular alterations and association with clinical parameters |
| 856 | 4 | 0 | |u https://doi.org/10.1371/journal.pone.0121980 |x Verlag |x Resolving-System |z kostenfrei |3 Volltext |
| 856 | 4 | 0 | |u https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0121980 |x Verlag |z kostenfrei |3 Volltext |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1371/journal.pone.0121980 |x Verlag |x Resolving-System |z kostenfrei |3 Volltext |
| 856 | 4 | 0 | |u http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4376900/ |x Verlag |z kostenfrei |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20170816 | ||
| 993 | |a Article | ||
| 994 | |a 2015 | ||
| 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 12 |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 10 | ||
| 998 | |g 131506641 |a Tariverdian, Mirjam |m 131506641:Tariverdian, Mirjam |d 910000 |d 910200 |e 910000PT131506641 |e 910200PT131506641 |k 0/910000/ |k 1/910000/910200/ |p 9 | ||
| 998 | |g 12390384X |a Schneider, Martin |m 12390384X:Schneider, Martin |d 910000 |d 910200 |e 910000PS12390384X |e 910200PS12390384X |k 0/910000/ |k 1/910000/910200/ |p 8 | ||
| 998 | |g 123210615 |a Grabe, Niels |m 123210615:Grabe, Niels |d 700000 |d 716000 |e 700000PG123210615 |e 716000PG123210615 |k 0/700000/ |k 1/700000/716000/ |p 7 | ||
| 998 | |g 1022879715 |a Lahrmann, Bernd |m 1022879715:Lahrmann, Bernd |d 700000 |d 716000 |e 700000PL1022879715 |e 716000PL1022879715 |k 0/700000/ |k 1/700000/716000/ |p 6 | ||
| 998 | |g 1012483967 |a Werft, Wiebke |m 1012483967:Werft, Wiebke |d 910000 |d 910100 |e 910000PW1012483967 |e 910100PW1012483967 |k 0/910000/ |k 1/910000/910100/ |p 5 | ||
| 998 | |g 106584686X |a Benner, Axel |m 106584686X:Benner, Axel |d 50000 |e 50000PB106584686X |k 0/50000/ |p 4 | ||
| 998 | |g 1138292184 |a Nelius, Nina |m 1138292184:Nelius, Nina |d 910000 |d 912000 |e 910000PN1138292184 |e 912000PN1138292184 |k 0/910000/ |k 1/910000/912000/ |p 3 | ||
| 998 | |g 1077930208 |a Echterdiek, Fabian Friedrich |m 1077930208:Echterdiek, Fabian Friedrich |d 50000 |e 50000PE1077930208 |k 0/50000/ |p 2 | ||
| 998 | |g 1068352116 |a Staffa, Laura |m 1068352116:Staffa, Laura |d 910000 |d 912000 |e 910000PS1068352116 |e 912000PS1068352116 |k 0/910000/ |k 1/910000/912000/ |p 1 |x j | ||
| 999 | |a KXP-PPN1562474103 |e 2977816070 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"id":{"doi":["10.1371/journal.pone.0121980"],"eki":["1562474103"]},"origin":[{"dateIssuedKey":"2015","dateIssuedDisp":"March 27, 2015"}],"relHost":[{"origin":[{"dateIssuedDisp":"2006-","dateIssuedKey":"2006","publisherPlace":"San Francisco, California, US ; Lawrence, Kan.","publisher":"PLOS ; PLoS"}],"part":{"text":"10(2015), 3, Artikel-ID e0121980, Seite 1-15","issue":"3","volume":"10","pages":"1-15","year":"2015","extent":"15"},"id":{"zdb":["2267670-3"],"issn":["1932-6203"],"eki":["523574592"]},"title":[{"title_sort":"PLOS ONE","title":"PLOS ONE"}],"name":{"displayForm":["Public Library of Science"]},"pubHistory":["1.2006 -"],"language":["eng"],"corporate":[{"display":"Public Library of Science","roleDisplay":"Herausgebendes Organ","role":"isb"}],"recId":"523574592","physDesc":[{"extent":"Online-Ressource"}],"note":["Schreibweise des Titels bis 2012: PLoS ONE","Gesehen am 20.03.19"],"disp":"Mismatch repair-deficient crypt foci in Lynch syndrome molecular alterations and association with clinical parametersPLOS ONE","type":{"bibl":"periodical","media":"Online-Ressource"}}],"physDesc":[{"extent":"15 S.","noteIll":"Illustrationen"}],"recId":"1562474103","language":["eng"],"note":["Gesehen am 29.10.2024"],"person":[{"family":"Staffa","given":"Laura","roleDisplay":"VerfasserIn","role":"aut","display":"Staffa, Laura"},{"role":"aut","roleDisplay":"VerfasserIn","display":"Echterdiek, Fabian Friedrich","family":"Echterdiek","given":"Fabian Friedrich"},{"family":"Nelius","given":"Nina","display":"Nelius, Nina","role":"aut","roleDisplay":"VerfasserIn"},{"family":"Benner","given":"Axel","display":"Benner, Axel","roleDisplay":"VerfasserIn","role":"aut"},{"given":"Wiebke","family":"Werft","role":"aut","roleDisplay":"VerfasserIn","display":"Werft, Wiebke"},{"display":"Lahrmann, Bernd","role":"aut","roleDisplay":"VerfasserIn","given":"Bernd","family":"Lahrmann"},{"family":"Grabe","given":"Niels","display":"Grabe, Niels","role":"aut","roleDisplay":"VerfasserIn"},{"family":"Schneider","given":"Martin","role":"aut","roleDisplay":"VerfasserIn","display":"Schneider, Martin"},{"family":"Tariverdian","given":"Mirjam","display":"Tariverdian, Mirjam","roleDisplay":"VerfasserIn","role":"aut"},{"family":"Knebel Doeberitz","given":"Magnus von","display":"Knebel Doeberitz, Magnus von","roleDisplay":"VerfasserIn","role":"aut"},{"given":"Matthias","family":"Kloor","display":"Kloor, Matthias","role":"aut","roleDisplay":"VerfasserIn"}],"type":{"bibl":"article-journal","media":"Online-Ressource"},"title":[{"title_sort":"Mismatch repair-deficient crypt foci in Lynch syndrome","title":"Mismatch repair-deficient crypt foci in Lynch syndrome","subtitle":"molecular alterations and association with clinical parameters"}],"name":{"displayForm":["Laura Staffa, Fabian Echterdiek, Nina Nelius, Axel Benner, Wiebke Werft, Bernd Lahrmann, Niels Grabe, Martin Schneider, Mirjam Tariverdian, Magnus von Knebel Doeberitz, Hendrik Bläker, Matthias Kloor"]}} | ||
| SRT | |a STAFFALAURMISMATCHRE2720 | ||