Related Experiment Video

Updated: Jul 10, 2025

Comprehensive DNA Methylation Analysis Using a Methyl-CpG-binding Domain Capture-based Method in Chronic Lymphocytic Leukemia Patients
13:21

Comprehensive DNA Methylation Analysis Using a Methyl-CpG-binding Domain Capture-based Method in Chronic Lymphocytic Leukemia Patients

Published on: June 16, 2017

10.1K

MLH1 Promoter Methylation Could Be the Second Hit in Lynch Syndrome Carcinogenesis

Ileana Wanda Carnevali1,2, Giulia Cini3, Laura Libera2,4

  • 1UO Anatomia Patologica Ospedale di Circolo ASST-Settelaghi, 21100 Varese, Italy.

Genes
|November 25, 2023
PubMed

Insights

MLH1 hypermethylation, often seen as sporadic, also occurs in Lynch syndrome cancers. This finding impacts colorectal and endometrial cancer screening protocols, requiring consideration of family history.

Area of Science:

  • Oncology
  • Epigenetics
  • Cancer Genetics

Background:

  • MLH1 hypermethylation is an epigenetic alteration linked to colorectal cancer (CRC) and endometrial cancer (EC) tumorigenesis, causing gene silencing and microsatellite instability.
  • MLH1 hypermethylation is typically viewed as a sporadic event, aiding in distinguishing sporadic cancers from inherited conditions like Lynch syndrome (LS).
  • However, rare instances of MLH1 hypermethylation have been documented in LS patients with CRC and EC.

Purpose of the Study:

  • To investigate the occurrence and significance of MLH1 hypermethylation in cancers from patients undergoing genetic counseling.
  • To determine if MLH1 hypermethylation is exclusively a sporadic event or if it also presents in Lynch syndrome-associated cancers.

Main Methods:

  • Analyzed 61 cancers (31 CRCs, 27 ECs, 2 ovarian, 1 stomach) from 56 patients for MLH1 protein loss and microsatellite instability.
  • Investigated MLH1 promoter methylation and MLH1/PMS2 germline variants in all selected cases.

Main Results:

  • Somatic MLH1 promoter hypermethylation was detected in 16.7% of CRC and 40% of EC cases with MLH1 germline pathogenic variants.
  • Primary and secondary MLH1 epimutations were identified in two families, indicating complex inheritance patterns.

Conclusions:

  • MLH1 hypermethylation is not solely a sporadic cancer mechanism; a notable proportion of Lynch syndrome-related cancers exhibit MLH1 hypermethylation.
  • Current universal Lynch syndrome screening protocols incorporating MLH1 methylation testing should be carefully applied, considering individual patient and family history.
Keywords:
LS universal screeningLynch syndromeMLH1 methylationconstitutional epimutation

More Related Videos

LINE-1 Methylation Analysis in Mesenchymal Stem Cells Treated with Osteosarcoma-Derived Extracellular Vesicles12:18

LINE-1 Methylation Analysis in Mesenchymal Stem Cells Treated with Osteosarcoma-Derived Extracellular Vesicles

Published on: February 1, 2020

5.8K
Methyl-binding DNA capture Sequencing for Patient Tissues08:40

Methyl-binding DNA capture Sequencing for Patient Tissues

Published on: October 31, 2016

8.7K

Related Concept Videos

Epigenetic Regulation01:46

Epigenetic Regulation

Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
31.1K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
Non-LTR Retrotransposons03:18

Non-LTR Retrotransposons

As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
11.5K
Mismatch Repair01:20

Mismatch Repair

Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
4.9K