Associated Genetic Biomarkers
Associated Diseases
Associated Pathways

Overview

Location [1]
3p22.2
Pathway
DNA damage/repair
Protein [2]
DNA mismatch repair protein Mlh1
Synonyms [1]
MMRCS1, HNPCC, FCC2, COCA2, HNPCC2, hMLH1

The mutL homolog 1 (MLH1) gene encodes a protein that functions in the DNA-mismatch repair process. Missense mutations, nonsense mutations, silent mutations, frameshift deletions and insertions, and in-frame deletions are observed in cancers such as endometrial cancer, intestinal cancer, and skin cancer.

MLH1 is altered in 1.28% of all cancers with colon adenocarcinoma, lung adenocarcinoma, endometrial endometrioid adenocarcinoma, breast invasive ductal carcinoma, and conventional glioblastoma multiforme having the greatest prevalence of alterations [3].

MLH1 GENIE Cases - Top Diseases

The most common alterations in MLH1 are MLH1 Mutation (1.00%), MLH1 Nonsense (0.15%), MLH1 Loss (0.07%), MLH1 Amplification (0.05%), and MLH1 R385C (0.03%) [3].

MLH1 GENIE Cases - Top Alterations

Biomarker-Directed Therapies

Significance of MLH1 in Diseases

Malignant Solid Tumor +

Colorectal Carcinoma +

Endometrial Carcinoma +

Endometrial Adenocarcinoma +

Non-Small Cell Lung Carcinoma +

Melanoma +

Head And Neck Squamous Cell Carcinoma +

Urothelial Carcinoma +

Breast Carcinoma +

Renal Cell Carcinoma +

Gastric Carcinoma +

Cervical Carcinoma +

Hepatocellular Carcinoma +

Adenocarcinoma Of The Gastroesophageal Junction +

Small Cell Lung Carcinoma +

Ovarian Carcinoma +

Merkel Cell Carcinoma +

Prostate Adenocarcinoma +

Gastric Adenocarcinoma +

Bladder Carcinoma +

Prostate Carcinoma +

Mesothelioma +

Esophageal Carcinoma +

Skin Squamous Cell Carcinoma +

Pancreatic Carcinoma +

Colorectal Adenocarcinoma +

Head And Neck Carcinoma +

Fallopian Tube Carcinoma +

Primary Peritoneal Carcinoma +

Classical Hodgkin Lymphoma +

Anal Carcinoma +

Esophageal Squamous Cell Carcinoma +

Cholangiocarcinoma +

Basal Cell Carcinoma +

Soft Tissue Sarcoma +

Pancreatic Ductal Adenocarcinoma +

Malignant Uterine Neoplasm +

Colon Adenocarcinoma +

Colon Carcinoma +

Squamous Cell Carcinoma +

Cutaneous Melanoma +

Hodgkin Lymphoma +

Nasopharyngeal Carcinoma +

Rectal Adenocarcinoma +

Endometrial Serous Adenocarcinoma +

Diffuse Large B-Cell Lymphoma +

High Grade Ovarian Serous Adenocarcinoma +

Esophagogastric Carcinoma +

Thyroid Gland Carcinoma +

Biliary Tract Carcinoma +

Pancreatic Adenocarcinoma +

Salivary Gland Carcinoma +

Vulvar Carcinoma +

Endometrial Undifferentiated Carcinoma +

Cervical Squamous Cell Carcinoma +

Endometrial Endometrioid Adenocarcinoma +

Squamous Cell Carcinoma Of The Penis +

Ovarian Endometrioid Adenocarcinoma +

Endometrial Clear Cell Adenocarcinoma +

High Grade Fallopian Tube Serous Adenocarcinoma +

Anal Squamous Cell Carcinoma +

Bladder Urothelial Carcinoma +

Thymic Carcinoma +

Glioma +

Central Nervous System Neoplasm +

Gallbladder Carcinoma +

Cancer +

Neuroendocrine Carcinoma +

Lung Adenocarcinoma +

Malignant Ovarian Epithelial Tumor +

Non-Clear Cell Renal Cell Carcinoma +

Lymphoma +

Non-Hodgkin Lymphoma +

Sarcoma +

Intrahepatic Cholangiocarcinoma +

Adnexal Carcinoma +

Anal Canal Squamous Cell Carcinoma +

Lynch Syndrome +

Vaginal Carcinoma +

Endometrial Mixed Adenocarcinoma +

Penile Carcinoma +

Endometrioid Adenocarcinoma +

Skin Carcinoma +

Malignant Uterine Corpus Neoplasm +

Laryngeal Squamous Cell Carcinoma +

Malignant Small Intestinal Neoplasm +

Oropharyngeal Squamous Cell Carcinoma +

Small Intestinal Adenocarcinoma +

Malignant Intestinal Neoplasm +

Ovarian Endometrioid Tumor +

Malignant Glioma +

Glioblastoma +

Uterine Corpus Carcinosarcoma +

Undifferentiated Pleomorphic Sarcoma +

Multiple Myeloma +

Mucosal Melanoma +

Peritoneal Mesothelioma +

Thymoma +

Malignant Gastric Neoplasm +

Appendix Carcinoma +

Carcinosarcoma +

Medulloblastoma +

Carcinoma +

Adenocarcinoma +

Carcinoma Of Unknown Primary +

Oral Cavity Squamous Cell Carcinoma +

Bone Sarcoma +

Clear Cell Renal Cell Carcinoma +

Acral Lentiginous Melanoma +

Malignant Esophagogastric Neoplasm +

Squamous Cell Lung Carcinoma +

Malignant Brain Neoplasm +

Malignant Pleural Mesothelioma +

Lung Neuroendocrine Neoplasm +

Pleural Mesothelioma +

Lung Carcinoma +

Non-Squamous Non-Small Cell Lung Carcinoma +

B-Cell Non-Hodgkin Lymphoma +

Chondrosarcoma +

Extrahepatic Cholangiocarcinoma +

Mature T-Cell And NK-Cell Non-Hodgkin Lymphoma +

Ampulla Of Vater Carcinoma +

Mantle Cell Lymphoma +

Ewing Sarcoma +

Ovarian Clear Cell Tumor +

Bile Duct Carcinoma +

Gastrointestinal Stromal Tumor +

Liposarcoma +

Osteosarcoma +

Malignant Salivary Gland Neoplasm +

Acute Myeloid Leukemia +

Leiomyosarcoma +

Appendix Neuroendocrine Tumor +

Bronchogenic Carcinoma +

Colon Neuroendocrine Neoplasm +

Desmoid-Type Fibromatosis +

Ependymoma +

Fallopian Tube Clear Cell Adenocarcinoma +

Fallopian Tube Endometrioid Adenocarcinoma +

Gallbladder Adenocarcinoma +

High-Grade Endometrial Stromal Sarcoma +

Hypopharyngeal Squamous Cell Carcinoma +

Mediastinal Large B-Cell Lymphoma +

Ocular Melanoma +

Ovarian Clear Cell Adenocarcinoma +

Ovarian Endometrioid Adenocarcinofibroma +

Pecoma +

Pancreatic Neuroendocrine Tumor +

Primary Mediastinal B-Cell Lymphoma +

Primary Peritoneal Clear Cell Carcinoma +

Primary Peritoneal Endometrioid Adenocarcinoma +

Primary Peritoneal High Grade Serous Adenocarcinoma +

Primary Peritoneal Serous Adenocarcinoma +

Rectal Neuroendocrine Tumor +

Small Intestinal Neuroendocrine Tumor +

Undifferentiated (Embryonal) Sarcoma +

Ureter Urothelial Carcinoma +

Vulvar Squamous Cell Carcinoma +

References

1. Hart R and Prlic A. Universal Transcript Archive Repository. Version uta_20180821. San Francisco CA: Github;2015. https://github.com/biocommons/uta

2. The UniProt Consortium. UniProt: a worldwide hub of protein knowledge. Nucleic Acids Research. 2019;47:D506-D515.

3. The AACR Project GENIE Consortium. AACR Project GENIE: powering precision medicine through an international consortium. Cancer Discovery. 2017;7(8):818-831. Dataset Version 8. This dataset does not represent the totality of the genetic landscape; see paper for more information.

4. All assertions and clinical trial landscape data are curated from primary sources. You can read more about the curation process here.