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http://hdl.handle.net/2445/198672
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DC Field | Value | Language |
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dc.contributor.author | Hitchins, Megan P. | - |
dc.contributor.author | Álvarez, Rocío | - |
dc.contributor.author | Zhou, Lisa | - |
dc.contributor.author | Aguirre, Francesca | - |
dc.contributor.author | Dámaso, Estela | - |
dc.contributor.author | Pineda Riu, Marta | - |
dc.contributor.author | Capella, Gabriel | - |
dc.contributor.author | Wong, Justin J.- L. | - |
dc.contributor.author | Yuan, Xiaopu | - |
dc.contributor.author | Ryan, Shawnia R. | - |
dc.contributor.author | Sathe, Devika S. | - |
dc.contributor.author | Baxter, Melanie D. | - |
dc.contributor.author | Cannon, Timothy | - |
dc.contributor.author | Biswas, Rakesh | - |
dc.contributor.author | Demarco, Tiffani | - |
dc.contributor.author | Grzelak, Doreen | - |
dc.contributor.author | Hampel, Heather | - |
dc.contributor.author | Pearlman, Rachel | - |
dc.date.accessioned | 2023-05-30T11:55:43Z | - |
dc.date.available | 2023-05-30T11:55:43Z | - |
dc.date.issued | 2023-04-01 | - |
dc.identifier.issn | 0090-8258 | - |
dc.identifier.uri | http://hdl.handle.net/2445/198672 | - |
dc.description.abstract | Objective. Universal screening of endometrial carcinoma (EC) for mismatch repair deficiency (MMRd) and Lynch syndrome uses presence of MLH1 methylation to omit common sporadic cases from follow-up germline testing. However, this overlooks rare cases with high-risk constitutional MLH1 methylation (epimutation), a poorly-recognized mechanism that predisposes to Lynch-type cancers with MLH1 methylation. We aimed to de-termine the role and frequency of constitutional MLH1 methylation among EC cases with MMRd, MLH1- methylated tumors.Methods. We screened blood for constitutional MLH1 methylation using pyrosequencing and real-time methylation-specific PCR in patients with MMRd, MLH1-methylated EC ascertained from (i) cancer clinics (n = 4, <60 years), and (ii) two population-based cohorts; Columbus-area (n = 68, all ages) and Ohio Colo-rectal Cancer Prevention Initiative (OCCPI) (n = 24, <60 years).Results. Constitutional MLH1 methylation was identified in three out of four patients diagnosed between 36 and 59 years from cancer clinics. Two had mono-/hemiallelic epimutation (similar to 50% alleles methylated). One with multiple primaries had low-level mosaicism in normal tissues and somatic second-hits affecting the unmethylated allele in all tumors, demonstrating causation. In the population-based cohorts, all 68 cases from the Columbus-area cohort were negative and low-level mosaic constitutional MLH1 methylation was identified in one patient aged 36 years out of 24 from the OCCPI cohort, representing one of six (similar to 17%) patients <50 years and one of 45 patients (similar to 2%) <60 years in the combined cohorts. EC was the first/dual-first cancer in three pa-tients with underlying constitutional MLH1 methylation.Conclusions. A correct diagnosis at first presentation of cancer is important as it will significantly alter clinical management. Screening for constitutional MLH1 methylation is warranted in patients with early-onset EC or syn-chronous/metachronous tumors (any age) displaying MLH1 methylation.(c) 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/). | - |
dc.format.extent | 12 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Elsevier | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1016/j.ygyno.2023.02.017 | - |
dc.relation.ispartof | Gynecologic Oncology, 2023, vol. 171, p. 129-140 | - |
dc.relation.uri | https://doi.org/10.1016/j.ygyno.2023.02.017 | - |
dc.rights | cc by-nc-nd (c) Hitchins, Megan P. et al, 2023 | - |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/es/ | * |
dc.source | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) | - |
dc.subject.classification | Càncer d'endometri | - |
dc.subject.classification | Medicina experimental | - |
dc.subject.other | Endometrial cancer | - |
dc.subject.other | Experimental medicine | - |
dc.title | MLH1-methylated endometrial cancer under 60 years of age as the “sentinel” cancer in female carriers of high-risk constitutional MLH1 epimutation | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.date.updated | 2023-05-29T12:10:44Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 36893489 | - |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
Files in This Item:
File | Description | Size | Format | |
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PIIS009082582300094X.pdf | 4.12 MB | Adobe PDF | View/Open |
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