Evidence map›Paper›PMID 42269807›Full record

ArticleCancer letters2026

The germline MLH1 c.2054 C>T mutation disrupts DNA mismatch repair and is detectable by digital PCR.

Matthew R Moldenhauer, Aditya Mahadevan, Cameron Hom, Angie T M Nguyen, Valeria Rangel, Sophie Hasson, Ning-Hsiang Hsu, Chimezie Ubbaonu, Deepika Nathan, Vishal S Chandan and 10 more

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In one paragraph

Article in Cancer letters, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors.

Matthew R MoldenhauerSchool of Medicine, University of California Irvine, Irvine, CA, USA.
Aditya MahadevanSchool of Medicine, University of California Irvine, Irvine, CA, USA.
Cameron HomSchool of Medicine, University of California Irvine, Irvine, CA, USA; Division of Hematology/Oncology, Department of Medicine, University of California Irvine, Orange, CA, USA; Department of Biological Chemistry, University of California Irvine, Irvine, CA, USA.
Angie T M NguyenSchool of Medicine, University of California Irvine, Irvine, CA, USA; Division of Hematology/Oncology, Department of Medicine, University of California Irvine, Orange, CA, USA; Department of Biological Chemistry, University of California Irvine, Irvine, CA, USA.
Valeria RangelSchool of Medicine, University of California Irvine, Irvine, CA, USA; Division of Hematology/Oncology, Department of Medicine, University of California Irvine, Orange, CA, USA; Department of Biological Chemistry, University of California Irvine, Irvine, CA, USA.
Sophie HassonSchool of Medicine, University of California Irvine, Irvine, CA, USA; Division of Hematology/Oncology, Department of Medicine, University of California Irvine, Orange, CA, USA.
Ning-Hsiang HsuSchool of Medicine, University of California Irvine, Irvine, CA, USA; Department of Biological Chemistry, University of California Irvine, Irvine, CA, USA.
Chimezie UbbaonuSchool of Medicine, University of California Irvine, Irvine, CA, USA; Division of Hematology/Oncology, Department of Medicine, University of California Irvine, Orange, CA, USA.
Deepika NathanSchool of Medicine, University of California Irvine, Irvine, CA, USA.
Vishal S ChandanSchool of Medicine, University of California Irvine, Irvine, CA, USA; Department of Pathology, University of California, Irvine, Orange, CA, USA.
Kaiyuan V ShenSchool of Medicine, University of California Irvine, Irvine, CA, USA; Division of Hematology/Oncology, Department of Medicine, University of California Irvine, Orange, CA, USA; Department of Biological Chemistry, University of California Irvine, Irvine, CA, USA; Institute for Immunology, University of California, Irvine, CA, USA.
Ellianna M DamozonioSchool of Medicine, University of California Irvine, Irvine, CA, USA; Division of Hematology/Oncology, Department of Medicine, University of California Irvine, Orange, CA, USA; Department of Biological Chemistry, University of California Irvine, Irvine, CA, USA.
Grace G ZhouSchool of Medicine, University of California Irvine, Irvine, CA, USA; Division of Hematology/Oncology, Department of Medicine, University of California Irvine, Orange, CA, USA.
Tanvi ChichiliCharlie Dunlop School of Biological Sciences, University of California, Irvine, CA, USA.
An LeCharlie Dunlop School of Biological Sciences, University of California, Irvine, CA, USA.
Selma MasriSchool of Medicine, University of California Irvine, Irvine, CA, USA; Department of Biological Chemistry, University of California Irvine, Irvine, CA, USA; Institute for Immunology, University of California, Irvine, CA, USA; Chao Family Comprehensive Cancer Center, University of California, Irvine, CA, USA.
Farshid DayyaniSchool of Medicine, University of California Irvine, Irvine, CA, USA; Division of Hematology/Oncology, Department of Medicine, University of California Irvine, Orange, CA, USA; Chao Family Comprehensive Cancer Center, University of California, Irvine, CA, USA.
Feng QiaoSchool of Medicine, University of California Irvine, Irvine, CA, USA; Department of Biological Chemistry, University of California Irvine, Irvine, CA, USA; Chao Family Comprehensive Cancer Center, University of California, Irvine, CA, USA.
Jennifer B ValerinSchool of Medicine, University of California Irvine, Irvine, CA, USA; Division of Hematology/Oncology, Department of Medicine, University of California Irvine, Orange, CA, USA; Chao Family Comprehensive Cancer Center, University of California, Irvine, CA, USA. Electronic address: jvalerin@hs.uci.edu.
Nicholas R PannunzioSchool of Medicine, University of California Irvine, Irvine, CA, USA; Division of Hematology/Oncology, Department of Medicine, University of California Irvine, Orange, CA, USA; Department of Biological Chemistry, University of California Irvine, Irvine, CA, USA; Institute for Immunology, University of California, Irvine, CA, USA; Chao Family Comprehensive Cancer Center, University of California, Irvine, CA, USA. Electronic address: nrpann@hs.uci.edu.

Funding

Univ.of Calif., Irvine Cancer Center Support GrantP30CA062203 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Melanie Funes · 1994 to 2026
$57.9M
CARCINOGENESIST32CA009054 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI EDINGER, AIMEE L, FRUMAN, DAVID ALEXANDER · 1985 to 2025
$8.6M
Circadian Clock and Myc-dependent Regulation of Cellular TransformationR01CA259370 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Selma Masri · 2022 to 2026
$3.0M
Rapid detection of CRLF2 rearrangements in Hispanic Ph-like ALL patients to access diagnosis and relapseR37CA266042 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Nicholas Pannunzio · 2022 to 2026
$2.5M
Aberrant V(D)J recombination in B cells initiates lymphoid malignancyR01CA276470 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Nicholas Pannunzio · 2024 to 2026
$1.0M
Immunology Research Training GrantT32AI177324 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI Eric Pearlman · 2023 to 2026
$735k
NCI NIH HHS P30 CA062203NCI NIH HHS R01 CA259370NCI NIH HHS R01 CA276470NCI NIH HHS R37 CA266042NCI NIH HHS T32 CA009054NIAID NIH HHS T32 AI177324
6 · The paper itself

Abstract

Lynch syndrome significantly increases the risk of developing colorectal cancer (CRC) due to an inherited defect in mismatch repair (MMR). Early detection relies on the identification of pathogenic mutations in patients with a family history of cancer, but few canonical Lynch mutations exist. Here, we describe four CRC patients found to carry an identical mutation in the MLH1 gene. Despite a strong family history of cancer, the MLH1 mutation was labeled discordantly regarding pathogenic potential. This highlights the need for improved diagnostics to screen for non-canonical Lynch variants. In addition to designing a novel digital PCR (dPCR) assay to rapidly detect MLH1 gene variants, we conducted in-depth analyses via molecular modeling, mutational signature analyses, and functional genetic assays to demonstrate that the MLH1 mutation results in a definitive MMR defect that increases cancer risk. This study emphasizes the need for improved diagnostic tools to identify pathogenic mutations in diverse populations.

Indexed as

Adaptor Proteins, Signal TransducingColorectal Neoplasms, Hereditary NonpolyposisDNA Mismatch RepairGerm-Line MutationMutL Protein Homolog 1Polymerase Chain ReactionAgedColorectal NeoplasmsDNA Mutational AnalysisFemaleGenetic Predisposition to DiseaseHumansMaleMiddle AgedPedigreeAdaptor Proteins, Signal TransducingMLH1 protein, humanMutL Protein Homolog 1

Identifiers

PMID42269807
PMCPMC13455714

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