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]
HNPCC2, FCC2, HNPCC, hMLH1, COCA2

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 Adenocarcinoma +

Non-Small Cell Lung Carcinoma +

Melanoma +

Head And Neck Squamous Cell Carcinoma +

Urothelial Carcinoma +

Renal Cell Carcinoma +

Breast Carcinoma +

Endometrial Carcinoma +

Gastric Carcinoma +

Cervical Carcinoma +

Small Cell Lung Carcinoma +

Hepatocellular Carcinoma +

Adenocarcinoma Of The Gastroesophageal Junction +

Merkel Cell Carcinoma +

Ovarian Carcinoma +

Prostate Adenocarcinoma +

Prostate Carcinoma +

Bladder Carcinoma +

Gastric Adenocarcinoma +

Mesothelioma +

Skin Squamous Cell Carcinoma +

Esophageal Carcinoma +

Pancreatic Carcinoma +

Fallopian Tube Carcinoma +

Head And Neck Carcinoma +

Primary Peritoneal Carcinoma +

Classical Hodgkin Lymphoma +

Colorectal Adenocarcinoma +

Cholangiocarcinoma +

Basal Cell Carcinoma +

Anal Carcinoma +

Soft Tissue Sarcoma +

Endometrial Clear Cell Adenocarcinoma +

Colon Adenocarcinoma +

Colon Carcinoma +

Cutaneous Melanoma +

Hodgkin Lymphoma +

Nasopharyngeal Carcinoma +

Rectal Adenocarcinoma +

Endometrial Serous Adenocarcinoma +

Diffuse Large B-Cell Lymphoma +

Cancer +

Esophagogastric Carcinoma +

Thyroid Gland Carcinoma +

Non-Hodgkin Lymphoma +

Biliary Tract Carcinoma +

Pancreatic Adenocarcinoma +

Salivary Gland Carcinoma +

Lynch Syndrome +

Endometrial Undifferentiated Carcinoma +

Cervical Squamous Cell Carcinoma +

Endometrial Endometrioid Adenocarcinoma +

Squamous Cell Carcinoma Of The Penis +

Pancreatic Ductal Adenocarcinoma +

Malignant Uterine Neoplasm +

Laryngeal Squamous Cell Carcinoma +

Anal Squamous Cell Carcinoma +

Bladder Urothelial Carcinoma +

Squamous Cell Carcinoma +

Thymic Carcinoma +

Glioma +

Central Nervous System Neoplasm +

Gallbladder Carcinoma +

Carcinosarcoma +

Oral Cavity Squamous Cell Carcinoma +

Neuroendocrine Carcinoma +

Clear Cell Renal Cell Carcinoma +

High Grade Ovarian Serous Adenocarcinoma +

Esophageal Squamous Cell Carcinoma +

Malignant Ovarian Epithelial Tumor +

Ovarian Clear Cell Tumor +

Sarcoma +

Adnexal Carcinoma +

Anal Canal Squamous Cell Carcinoma +

Vulvar Carcinoma +

Clear Cell Odontogenic Carcinoma +

Endometrial Mixed Adenocarcinoma +

Penile Carcinoma +

Endometrioid Adenocarcinoma +

Skin Carcinoma +

Ovarian Endometrioid Adenocarcinoma +

High Grade Fallopian Tube Serous Adenocarcinoma +

Malignant Small Intestinal Neoplasm +

Oropharyngeal Squamous Cell Carcinoma +

Pharyngeal Squamous Cell Carcinoma +

Malignant Intestinal Neoplasm +

Ovarian Endometrioid Tumor +

Malignant Glioma +

Glioblastoma +

Uterine Corpus Carcinosarcoma +

Undifferentiated Pleomorphic Sarcoma +

Mucosal Melanoma +

Peritoneal Mesothelioma +

Thymoma +

Malignant Gastric Neoplasm +

Appendix Carcinoma +

Medulloblastoma +

Carcinoma +

Clear Cell Adenocarcinoma +

Adenocarcinoma +

Carcinoma Of Unknown Primary +

Primary Cutaneous T Cell Non-Hodgkin Lymphoma +

Bone Sarcoma +

Kidney Carcinoma +

Malignant Esophagogastric Neoplasm +

Squamous Cell Lung Carcinoma +

Malignant Brain Neoplasm +

Malignant Pleural Mesothelioma +

Lung Neuroendocrine Neoplasm +

Pleural Mesothelioma +

Esophageal Adenocarcinoma +

Histiocytic And Dendritic Cell Neoplasm +

Lung Carcinoma +

Non-Squamous Non-Small Cell Lung Carcinoma +

Non-Clear Cell Renal Cell Carcinoma +

B-Cell Non-Hodgkin Lymphoma +

Chondrosarcoma +

Lymphoma +

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

Ampulla Of Vater Carcinoma +

Mantle Cell Lymphoma +

Ewing Sarcoma +

Malignant Ovarian Clear Cell Tumor +

Bile Duct Carcinoma +

Gastrointestinal Stromal Tumor +

Osteosarcoma +

Liposarcoma +

Intrahepatic Cholangiocarcinoma +

Malignant Salivary Gland Neoplasm +

Acute Myeloid Leukemia +

Leiomyosarcoma +

Ampulla Of Vater Clear Cell Adenocarcinoma +

Appendix Neuroendocrine Tumor +

Bladder Clear Cell Adenocarcinoma +

Bronchogenic Carcinoma +

Cervical Clear Cell Adenocarcinoma +

Clear Cell Hepatocellular Carcinoma +

Clear Cell Sarcoma Of Soft Tissue +

Clear Cell Sarcoma Of The Kidney +

Clear Cell Squamous Cell Skin Carcinoma +

Colorectal Neuroendocrine Tumor +

Constitutional Mismatch Repair Deficiency Syndrome +

Desmoid-Type Fibromatosis +

Ependymoma +

Extrahepatic Bile Duct Clear Cell Adenocarcinoma +

Fallopian Tube Clear Cell Adenocarcinoma +

Gallbladder Adenocarcinoma +

Hereditary Clear Cell Renal Cell Carcinoma +

High-Grade Endometrial Stromal Sarcoma +

Hypopharyngeal Squamous Cell Carcinoma +

Large Cell Lung Carcinoma, Clear Cell Variant +

Mediastinal Large B-Cell Lymphoma +

Ocular Melanoma +

Ovarian Endometrioid Adenocarcinofibroma +

Pecoma +

Pancreatic Neuroendocrine Tumor +

Primary Mediastinal B-Cell Lymphoma +

Primary Peritoneal Serous Adenocarcinoma +

Skin Basosquamous Cell Carcinoma +

Skin Clear Cell Basal Cell Carcinoma +

Small Intestinal Neuroendocrine Tumor +

Thymic Clear Cell Carcinoma +

Undifferentiated (Embryonal) Sarcoma +

Ureter Urothelial Carcinoma +

Urethral Clear Cell Adenocarcinoma +

Uterine Ligament Clear Cell Adenocarcinoma +

Uveal Melanoma +

Vaginal Carcinoma +

Vulvar Clear Cell Hidradenocarcinoma +

Vulvar Squamous Cell Carcinoma +

Xeroderma Pigmentosum +

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.