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@ARTICLE{Helderman:285997,
author = {N. C. Helderman and K. D. Andini and M. E. van Leerdam and
L. P. van Hest and D. R. Hoekman and A. Ahadova$^*$ and S.
W. Bajwa-Ten Broeke and T. Bosse and E. M. J. van der Logt
and F. Imhann and M. Kloor$^*$ and A. M. J. Langers and V.
T. H. B. M. Smit and D. Terlouw and T. van Wezel and H.
Morreau and M. Nielsen},
title = {{MLH}1 promotor hypermethylation in colorectal and
endometrial carcinomas from patients with {L}ynch syndrome.},
journal = {The journal of molecular diagnostics},
volume = {26},
number = {2},
issn = {1525-1578},
address = {Amsterdam [u.a.]},
publisher = {Elsevier},
reportid = {DKFZ-2023-02578},
pages = {106-114},
year = {2024},
note = {2024 Feb;26(2):106-114},
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.},
keywords = {Lynch syndrome (Other) / MLH1 promotor hypermethylation
(Other) / colorectal cancer (Other) / endometrial cancer
(Other) / genetic testing (Other) / immunohistochemistry
(Other) / mismatch repair (Other) / screening (Other)},
cin = {F210},
ddc = {610},
cid = {I:(DE-He78)F210-20160331},
pnm = {316 - Infektionen, Entzündung und Krebs (POF4-316)},
pid = {G:(DE-HGF)POF4-316},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:38061582},
doi = {10.1016/j.jmoldx.2023.10.005},
url = {https://inrepo02.dkfz.de/record/285997},
}