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BIOMARKER:

MLH3 mutation

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Other names: MutL Homolog 3, DNA Mismatch Repair Protein Mlh3, MutL (E. Coli) Homolog 3, MutL Homolog 3 (E. Coli), MutL Protein Homolog 3, HNPCC7
Entrez ID:
24d
In two independent genomic datasets from TCGA and Tianjin cohorts, low risk scores were associated with higher tumor mutation loads and improved outcome in patients with gastric adenocarcinoma. This finding may have implications for prognostic prediction and therapeutic guidance for gastric adenocarcinoma.
Journal • Tumor Mutational Burden
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TMB (Tumor Mutational Burden) • POLE (DNA Polymerase Epsilon) • MUC16 (Mucin 16, Cell Surface Associated)
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POLE mutation • MLH3 mutation • MUC16 mutation
2ms
Clinically, group-A and group-B behave like group-C, having better prognosis. Therefore, these patients may escape adjuvant therapy despite their TP53-mutant status. The subset of cases who would benefit from this comprise 8.41% (group-A + group-B = 18/214*100) of the TP53-mutant cases or 3.39% (group-A + group-B = 18/530*100) as opposed to the repoetedly acclaimed 1.69% (group-C = 9/530*100) of total cases.
TP53 (Tumor protein P53) • POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • MSH3 (MutS Homolog 3) • PMS1 (PMS1 protein homolog 1)
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TP53 mutation • POLE mutation • MSH2 mutation • MSH3 mutation • MLH3 mutation • PMS1 mutation • PMS2 mutation • TP53 Y220C
2ms
Somatic MMR mutations tend to increase TMB. Adequate investigation should be made to determine immunotherapy efficacy in these patients.
Tumor Mutational Burden • Microsatellite instability • MSi-H Biomarker • IO biomarker
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • POLE (DNA Polymerase Epsilon) • KMT2D (Lysine Methyltransferase 2D) • LRP1B (LDL Receptor Related Protein 1B) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • POLD1 (DNA Polymerase Delta 1) • FAT1 (FAT atypical cadherin 1) • MSH3 (MutS Homolog 3) • MLL2 (Myeloid/lymphoid or mixed-lineage leukemia 2)
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TP53 mutation • EGFR mutation • TMB-H • MSI-H/dMMR • HER-2 amplification • ALK fusion • KMT2D mutation • ROS1 fusion • MSH6 mutation • POLD1 mutation • MSH2 mutation • MLH1 mutation • MLH3 mutation • PMS2 mutation
5ms
Affected genes encode proteins involved in DNA repair (ATM, ATR, BRCA2, BRIP1, CHEK2, MLH3, MUTYH, POLE, POLE4, POLQ, XRCC1), chromatin modification (ARID1B, DNMT3A, JARID2, SETD1B) or other cellular pathways: LRRK2 (2 cases) and MSH4. Notably, somatic truncating mutation or deletions of LRRK2 were occasionally found in MMs in The Cancer Genome Atlas, and expression of LRRK2 was undetectable or downregulated in a majority of primary MMs and MM cell lines we examined, implying that loss of LRRK2 expression is a newly recognized tumor suppressor alteration in MM.
Journal • BRCA Biomarker
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BRCA2 (Breast cancer 2, early onset) • DNMT3A (DNA methyltransferase 1) • BAP1 (BRCA1 Associated Protein 1) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • ARID1B (AT-Rich Interaction Domain 1B) • MUTYH (MutY homolog) • MSH4 (MutS Homolog 4) • POLE4 (DNA Polymerase Epsilon 4 Accessory Subunit) • XRCC1 (X-Ray Repair Cross Complementing 1)
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BAP1 mutation • BRIP1 mutation • CHEK2 mutation • MLH3 mutation
7ms
A comprehensive molecular analysis of the primary tumor guided by histologic analysis may help to better stratify patients for precision medicine approaches. Given the association between the molecular and the histologic heterogeneity, the selection of tumor samples for molecular analysis should be based on meticulous histologic evaluation of the entire tumor.
Journal
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BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • NCOA4 (Nuclear Receptor Coactivator 4) • E2F1 (E2F transcription factor 1)
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BRAF mutation • NRAS mutation • MLH3 mutation
8ms
This initial study of WES of BBB shows its potential for the identification of genetic alterations that portend breast oncogenesis. In future larger studies, robust personalized breast cancer risk indicators leading to novel interception paradigms can be assessed.
Journal
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
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PIK3CA mutation • PIK3CA H1047R • MLH3 mutation
10ms
According to clinical results of LOXO-101, NTRK1 fusion with critical kinase domain had a good response to this inhibitor...Three novel partners (DPP10-, FRMPD1- and KMT2C-) were found in our cohort. Half of the NTRK1 fusion patients were co-mutated with EGFR activating mutations, which meaning that understanding of gene fusion mediating EGFR-TKI resistance is helpful to the development of follow-up treatment strategies.
EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • KMT2C (Lysine Methyltransferase 2C) • TPM3 (Tropomyosin 3) • LMNA (Lamin A/C) • NTRK (Neurotrophic receptor tyrosine kinase)
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TP53 mutation • BRAF V600E • EGFR mutation • BRAF V600 • NTRK1 fusion • PIK3CA mutation • EGFR L858R • TPM3-NTRK1 fusion • MSH2 mutation • PIK3CA E545 • EGFR G719C • MLH3 mutation • NTRK1 mutation • NTRK fusion
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Vitrakvi (larotrectinib)
12ms
No mutation was identified in RAD51, MRE11A, FAM175A, XRCC2, or MLH3. The involvement of these genes in the hereditary predisposition to cancer cannot be ruled out, although if it exists it is rare or does not seem to involve truncating variants.
Clinical • Journal
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RAD51B (RAD51 Paralog B) • RAD51 (RAD51 Homolog A) • MRE11A (MRE11 homolog, double strand break repair nuclease) • RAD50 (RAD50 Double Strand Break Repair Protein) • BARD1 (BRCA1 Associated RING Domain 1) • FANCM (FA Complementation Group M) • PMS1 (PMS1 protein homolog 1)
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RAD51B mutation • BARD1 mutation • MRE11A mutation • RAD50 mutation • MLH3 mutation • FANCM mutation • RAD51 mutation
1year
Our study proved heterogenous pattern of clonal evolution in gliomas which is characterized by acquisition of new genomic aberrations and leads to high genome instability. We proved, that recurrences are genetically/epigenetically different from their primaries and may arise from one major tumor clone or by one or more subclones presented within primary tumors.Supported by RVO-VFN64165
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
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IDH2 mutation • MLH3 mutation
over1year
This initial study of WES of BBB shows its potential for the identification of genetic alterations that portend breast oncogenesis. In future larger studies, robust personalized breast cancer risk indicators leading to novel interception paradigms can be assessed.
Journal
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
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PIK3CA mutation • PIK3CA H1047R • MLH3 mutation
over1year
Whole-genome sequencing may offer a technology for increasing this proportion, particularly if applied on pedigree data allowing linkage type of analysis. The final section critically surveys the large number of candidate genes that have been recently proposed for CRC predisposition.
Review • Journal
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RNF43 (Ring Finger Protein 43) • MSH3 (MutS Homolog 3)
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MLH3 mutation
over1year
Until very recently, FDA approved the first molecularly targeted therapy with the PARP inhibitor Olaparib for pancreatic cancer patients with germline mutations on BRCA1/2, two types of homologous recombination (HR)/DNA damage repair (DDR) genes...The BRCA1/2 germline mutations were found at low levels in our cohort (0.8%) compared to the American cohorts ( 2.4~2.7%), Furthermore, the whole DDR mutations exhibited highest proportion [10.5% (27/256) from our study, compared with 7.3% (21/289) from Yurgelun, and 5.4% (10/185) from TCGA, respectively].CONCLUSIONIn conclusion,our results characterized the germline mutation landscape of DDRs in the largest oriental cohort of pancreatic cancer to date, and first discovered two novel germline mutations in pancreatic cancer. Most importantly, nearly 10% of PDAC patients in this study were found to harbor germline DDR mutations, which may benefit more patients with an effective therapeutic synergy for PARP and PD-1 inhibitors in clinical practice.
BRCA Biomarker • PARP Biomarker • PD(L)-1 Biomarker • IO biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • MSH6 (MutS homolog 6) • ERCC2 (Excision repair cross-complementation group 2) • CHEK2 (Checkpoint kinase 2) • RAD54L (DNA Repair And Recombination Protein RAD54) • MUTYH (MutY homolog) • WRN (WRN RecQ Like Helicase)
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BRCA1 mutation • BRCA2 mutation • PALB2 mutation • MSH6 mutation • RAD54L mutation • MLH3 mutation
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Lynparza (olaparib)
over1year
Legal entity responsible for the study The authors. Funding Has not received any funding.
BRCA Biomarker
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BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • MSH2 (MutS Homolog 2) • RAD51B (RAD51 Paralog B) • CHEK2 (Checkpoint kinase 2) • CDH1 (Cadherin 1)
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BRCA2 mutation • PALB2 mutation • CHEK2 mutation • MSH2 mutation • RAD51B mutation • MLH3 mutation
over1year
EEC G3 harbored the most MMR mutations among EC. EEC G3 and USC could be more considered to screen MMR mutation due to more MMR mutations occurred in EEC G3 and USC than did among EEC G2 and EEC G1. Besides MLH1, MSH2, MSH6, PMS2 and EPCAM mutation, MLH3, MSH3, PMS1 mutation could be screened in patients with newly diagnosed endometrial carcinoma.
Clinical
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MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • MSH3 (MutS Homolog 3) • EPCAM (Epithelial cell adhesion molecule) • PMS1 (PMS1 protein homolog 1)
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MSH2 mutation • MSH3 mutation • MLH1 mutation • MLH3 mutation • PMS1 mutation • PMS2 mutation
over1year
Our study retrospectively analyzed germline mutation profile of prostate cancer in Chinese population. The frequency of HSD3B1 (1245C) allele varies across ethnic populations in spite of the similar DNA repair gene mutations rates. Considering the gene list should be tested based on clinical/familial scenarios from the Philadelphia Prostate Cancer Consensus Conference, a prevalence of certain mutations, G84E mutation in HOXB13 was unnecessary for genetic testing in Chinese population.
BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • ATR (Ataxia telangiectasia and Rad3-related protein) • RAD50 (RAD50 Double Strand Break Repair Protein) • MUTYH (MutY homolog) • PMS1 (PMS1 protein homolog 1) • FANCD2 (FA Complementation Group D2) • HOXB13 (Homeobox B13)
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BRCA2 mutation • PALB2 mutation • RAD50 mutation • MLH3 mutation
over1year
2.9% patients were identified as MSI-H in Chinese prostate patients. MSI-H was associated with higher TMB, SNVs and Indels. Targeted next-generation sequencing is a practical tool for prostate cancer genotyping and treatment decision-making.
Clinical • Tumor Mutational Burden • Microsatellite instability • MSi-H Biomarker • IO biomarker
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EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • KMT2D (Lysine Methyltransferase 2D) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • KMT2C (Lysine Methyltransferase 2C) • JAK1 (Janus Kinase 1) • PMS2 (PMS1 protein homolog 2)
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PTEN mutation • MSH6 mutation • MSH2 mutation • AR amplification • MLH3 mutation • PMS2 mutation
over1year
4.5% of patients carrying germline variants may be linked to increased susceptibility to lung cancer. The susceptibility is mainly reflected in family history and morbidity risk without significant influence on aberrant pathways. Research Funding: the Special Funds for Strategic Emerging Industry Development of Shenzhen (grant number 20170922151538732), the Science and Technology Project of Shenzhen (grant number JSGG20180703164202084)
BRCA Biomarker
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TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • PALB2 (Partner and localizer of BRCA2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD50 (RAD50 Double Strand Break Repair Protein) • EPCAM (Epithelial cell adhesion molecule)
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TP53 mutation • BRCA2 mutation • PALB2 mutation • BRIP1 mutation • CHEK2 mutation • RAD50 mutation • BLM mutation • MLH3 mutation