Journal Article

DKFZ-2023-02578

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png MLH1 promotor hypermethylation in colorectal and endometrial carcinomas from patients with Lynch syndrome.

Helderman, N. C. ; Andini, K. D. ; van Leerdam, M. E. ; van Hest, L. P. ; Hoekman, D. R. ; Ahadova, A.DKFZ* ; Bajwa-Ten Broeke, S. W. ; Bosse, T. ; van der Logt, E. M. J. ; Imhann, F. ; Kloor, M.DKFZ* ; Langers, A. M. J. ; Smit, V. T. H. B. M. ; Terlouw, D. ; van Wezel, T. ; Morreau, H. ; Nielsen, M.

2024
Elsevier Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.jmoldx.2023.10.005

Abstract: Screening for Lynch syndrome (LS) in colorectal cancer (CRC) and endometrial cancer (EC) patients generally involves immunohistochemical staining of the mismatch repair (MMR) proteins. In case of MLH1 protein loss, MLH1 promotor hypermethylation (MLH1-PM) testing is performed to indirectly distinguish constitutional MLH1 variants from somatic epimutations. However, in recent years a growing number of studies have reported that MLH1-PM and pathogenic constitutional MMR variants are not mutually exclusive. This study describes six new and 86 previously reported MLH1-PM CRCs or ECs in LS patients. Of these, methylation of the MLH1 gene promotor 'C region' was reported in 30 MLH1, six MSH2, six MSH6 and three PMS2 variant carriers at median ages at diagnosis of 48.5 (IQR 39-56.75), 39 (IQR 29-51), 58 (IQR 53.5-67) and 68 (IQR 65.6-68.5) years, respectively. For 31 MLH1-PM CRCs in LS patients from literature, only the 'B region' of the MLH1 gene promotor was tested, whereas for 13 literature cases the tested MLH1 gene promotor region was not specified. Collectively, these data indicate that a diagnosis of LS should not be excluded when MLH1-PM is detected. Clinicians should carefully consider whether or not follow-up genetic MMR gene testing should be offered, with age < 60-70 years and/or a positive family history amongst other factors being suggestive for a potential constitutional MMR gene defect.

Keyword(s): Lynch syndrome ; MLH1 promotor hypermethylation ; colorectal cancer ; endometrial cancer ; genetic testing ; immunohistochemistry ; mismatch repair ; screening

Note: 2024 Feb;26(2):106-114

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Contributing Institute(s):

1. KKE Angewandte Tumorbiologie (F210)

Research Program(s):

1. 316 - Infektionen, Entzündung und Krebs (POF4-316) (POF4-316)

Appears in the scientific report 2023

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Essential Science Indicators ; IF < 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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