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Deleterious MSH6 Gene Mutation

MedGen UID:
1385562
•Concept ID:
C4329708
•
Cell or Molecular Dysfunction
Synonyms: Deleterious HNPCC5 Gene Mutation; Deleterious MutS Homolog 6 Gene Mutation; Deleterious MutS, E. coli, Homolog of, 6 Gene Mutation

Definition

A change in the nucleotide sequence of the MSH6 gene that is associated with increased risk of disease. [from NCI]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVDeleterious MSH6 Gene Mutation

Professional guidelines

PubMed

Next Generation Sequencing in Molecular Diagnosis of Lynch Syndrome - a Pilot Study Using New Stratification Criteria.
Kašubová I, Holubeková V, Janíková K, Váňová B, Sňahničanová Z, Kalman M, Plank L, Lasabová Z
Acta Medica (Hradec Kralove) 2018;61(3):98-102. doi: 10.14712/18059694.2018.125. PMID: 30543514
Genotype-phenotype correlation in MMR mutation-positive families with Lynch syndrome.
Pérez-Cabornero L, Infante M, Velasco E, Lastra E, Miner C, Durán M
Int J Colorectal Dis 2013 Sep;28(9):1195-201. Epub 2013 Apr 16 doi: 10.1007/s00384-013-1685-x. PMID: 23588873
Current clinical criteria for Lynch syndrome are not sensitive enough to identify MSH6 mutation carriers.
Sjursen W, Haukanes BI, Grindedal EM, Aarset H, Stormorken A, Engebretsen LF, Jonsrud C, Bjørnevoll I, Andresen PA, Ariansen S, Lavik LA, Gilde B, Bowitz-Lothe IM, Maehle L, Møller P
J Med Genet 2010 Sep;47(9):579-85. Epub 2010 Jun 28 doi: 10.1136/jmg.2010.077677. PMID: 20587412Free PMC Article

Recent clinical studies

Etiology

Clinical and biological landscape of constitutional mismatch-repair deficiency syndrome: an International Replication Repair Deficiency Consortium cohort study.
Ercan AB, Aronson M, Fernandez NR, Chang Y, Levine A, Liu ZA, Negm L, Edwards M, Bianchi V, Stengs L, Chung J, Al-Battashi A, Reschke A, Lion A, Ahmad A, Lassaletta A, Reddy AT, Al-Darraji AF, Shah AC, Van Damme A, Bendel A, Rashid A, Margol AS, Kelly BL, Pencheva B, Heald B, Lemieux-Anglin B, Crooks B, Koschmann C, Gilpin C, Porter CC, Gass D, Samuel D, Ziegler DS, Blumenthal DT, Kuo DJ, Hamideh D, Basel D, Khuong-Quang DA, Stearns D, Opocher E, Carceller F, Baris Feldman H, Toledano H, Winer I, Scheers I, Fedorakova I, Su JM, Vengoechea J, Sterba J, Knipstein J, Hansford JR, Gonzales-Santos JR, Bhatia K, Bielamowicz KJ, Minhas K, Nichols KE, Cole KA, Penney L, Hjort MA, Sabel M, Gil-da-Costa MJ, Murray MJ, Miller M, Blundell ML, Massimino M, Al-Hussaini M, Al-Jadiry MF, Comito MA, Osborn M, Link MP, Zapotocky M, Ghalibafian M, Shaheen N, Mushtaq N, Waespe N, Hijiya N, Fuentes-Bolanos N, Ahmad O, Chamdine O, Roy P, Pichurin PN, Nyman P, Pearlman R, Auer RC, Sukumaran RK, Kebudi R, Dvir R, Raphael R, Elhasid R, McGee RB, Chami R, Noss R, Tanaka R, Raskin S, Sen S, Lindhorst S, Perreault S, Caspi S, Riaz S, Constantini S, Albert S, Chaleff S, Bielack S, Chiaravalli S, Cramer SL, Roy S, Cahn S, Penna S, Hamid SA, Ghafoor T, Imam U, Larouche V, Magimairajan Issai V, Foulkes WD, Lee YY, Nathan PC, Maruvka YE, Greer MC, Durno C, Shlien A, Ertl-Wagner B, Villani A, Malkin D, Hawkins C, Bouffet E, Das A, Tabori U
Lancet Oncol 2024 May;25(5):668-682. Epub 2024 Mar 26 doi: 10.1016/S1470-2045(24)00026-3. PMID: 38552658
Novel MSH6 mutation predicted metastasis in eyelid and periocular squamous cell carcinoma.
Luo Y, Rao Y, Gu X, Chai P, Yang Y, Lin J, Xu X, Jia R, Xu S
J Eur Acad Dermatol Venereol 2022 Dec;36(12):2331-2342. Epub 2022 Aug 23 doi: 10.1111/jdv.18454. PMID: 35855666
Whole exome profiling and mutational analysis of Ocular Surface Squamous Neoplasia.
Ramos-Betancourt N, Field MG, Davila-Alquisiras JH, Karp CL, Hernández-Zimbrón LF, García-Vázquez R, Vazquez-Romo KA, Wang G, Fromow-Guerra J, Hernandez-Quintela E, Galor A
Ocul Surf 2020 Oct;18(4):627-632. Epub 2020 Jul 24 doi: 10.1016/j.jtos.2020.07.011. PMID: 32717381Free PMC Article
Gene panel sequencing in familial breast/ovarian cancer patients identifies multiple novel mutations also in genes others than BRCA1/2.
Kraus C, Hoyer J, Vasileiou G, Wunderle M, Lux MP, Fasching PA, Krumbiegel M, Uebe S, Reuter M, Beckmann MW, Reis A
Int J Cancer 2017 Jan 1;140(1):95-102. Epub 2016 Sep 23 doi: 10.1002/ijc.30428. PMID: 27616075
Frequency of Germline Mutations in 25 Cancer Susceptibility Genes in a Sequential Series of Patients With Breast Cancer.
Tung N, Lin NU, Kidd J, Allen BA, Singh N, Wenstrup RJ, Hartman AR, Winer EP, Garber JE
J Clin Oncol 2016 May 1;34(13):1460-8. Epub 2016 Mar 14 doi: 10.1200/JCO.2015.65.0747. PMID: 26976419Free PMC Article

Diagnosis

Clinical and biological landscape of constitutional mismatch-repair deficiency syndrome: an International Replication Repair Deficiency Consortium cohort study.
Ercan AB, Aronson M, Fernandez NR, Chang Y, Levine A, Liu ZA, Negm L, Edwards M, Bianchi V, Stengs L, Chung J, Al-Battashi A, Reschke A, Lion A, Ahmad A, Lassaletta A, Reddy AT, Al-Darraji AF, Shah AC, Van Damme A, Bendel A, Rashid A, Margol AS, Kelly BL, Pencheva B, Heald B, Lemieux-Anglin B, Crooks B, Koschmann C, Gilpin C, Porter CC, Gass D, Samuel D, Ziegler DS, Blumenthal DT, Kuo DJ, Hamideh D, Basel D, Khuong-Quang DA, Stearns D, Opocher E, Carceller F, Baris Feldman H, Toledano H, Winer I, Scheers I, Fedorakova I, Su JM, Vengoechea J, Sterba J, Knipstein J, Hansford JR, Gonzales-Santos JR, Bhatia K, Bielamowicz KJ, Minhas K, Nichols KE, Cole KA, Penney L, Hjort MA, Sabel M, Gil-da-Costa MJ, Murray MJ, Miller M, Blundell ML, Massimino M, Al-Hussaini M, Al-Jadiry MF, Comito MA, Osborn M, Link MP, Zapotocky M, Ghalibafian M, Shaheen N, Mushtaq N, Waespe N, Hijiya N, Fuentes-Bolanos N, Ahmad O, Chamdine O, Roy P, Pichurin PN, Nyman P, Pearlman R, Auer RC, Sukumaran RK, Kebudi R, Dvir R, Raphael R, Elhasid R, McGee RB, Chami R, Noss R, Tanaka R, Raskin S, Sen S, Lindhorst S, Perreault S, Caspi S, Riaz S, Constantini S, Albert S, Chaleff S, Bielack S, Chiaravalli S, Cramer SL, Roy S, Cahn S, Penna S, Hamid SA, Ghafoor T, Imam U, Larouche V, Magimairajan Issai V, Foulkes WD, Lee YY, Nathan PC, Maruvka YE, Greer MC, Durno C, Shlien A, Ertl-Wagner B, Villani A, Malkin D, Hawkins C, Bouffet E, Das A, Tabori U
Lancet Oncol 2024 May;25(5):668-682. Epub 2024 Mar 26 doi: 10.1016/S1470-2045(24)00026-3. PMID: 38552658
Gene panel sequencing in familial breast/ovarian cancer patients identifies multiple novel mutations also in genes others than BRCA1/2.
Kraus C, Hoyer J, Vasileiou G, Wunderle M, Lux MP, Fasching PA, Krumbiegel M, Uebe S, Reuter M, Beckmann MW, Reis A
Int J Cancer 2017 Jan 1;140(1):95-102. Epub 2016 Sep 23 doi: 10.1002/ijc.30428. PMID: 27616075
Germline multi-gene hereditary cancer panel testing in an unselected endometrial cancer cohort.
Ring KL, Bruegl AS, Allen BA, Elkin EP, Singh N, Hartman AR, Daniels MS, Broaddus RR
Mod Pathol 2016 Nov;29(11):1381-1389. Epub 2016 Jul 22 doi: 10.1038/modpathol.2016.135. PMID: 27443514Free PMC Article
Frequency of Germline Mutations in 25 Cancer Susceptibility Genes in a Sequential Series of Patients With Breast Cancer.
Tung N, Lin NU, Kidd J, Allen BA, Singh N, Wenstrup RJ, Hartman AR, Winer EP, Garber JE
J Clin Oncol 2016 May 1;34(13):1460-8. Epub 2016 Mar 14 doi: 10.1200/JCO.2015.65.0747. PMID: 26976419Free PMC Article
Conversion analysis for mutation detection in MLH1 and MSH2 in patients with colorectal cancer.
Casey G, Lindor NM, Papadopoulos N, Thibodeau SN, Moskow J, Steelman S, Buzin CH, Sommer SS, Collins CE, Butz M, Aronson M, Gallinger S, Barker MA, Young JP, Jass JR, Hopper JL, Diep A, Bapat B, Salem M, Seminara D, Haile R; Colon Cancer Family Registry
JAMA 2005 Feb 16;293(7):799-809. doi: 10.1001/jama.293.7.799. PMID: 15713769Free PMC Article

Therapy

Anthracycline-related cardiotoxicity in patients with breast cancer harboring mutational signature of homologous recombination deficiency (HRD).
Incorvaia L, Badalamenti G, Novo G, Gori S, Cortesi L, Brando C, Cinieri S, Curigliano G, Ricciardi GR, Toss A, Chiari R, Berardi R, Ballatore Z, Bono M, Bazan Russo TD, Gristina V, Galvano A, Damerino G, Blasi L, Bazan V, Russo A
ESMO Open 2024 Jan;9(1):102196. Epub 2023 Dec 19 doi: 10.1016/j.esmoop.2023.102196. PMID: 38118367Free PMC Article
Complete response to anti-PD-L1 antibody in a metastatic bladder cancer associated with novel MSH4 mutation and microsatellite instability.
Yang Y, Jain RK, Glenn ST, Xu B, Singh PK, Wei L, Hu Q, Long M, Hutson N, Wang J, Battaglia S, George S
J Immunother Cancer 2020 Mar;8(1) doi: 10.1136/jitc-2019-000128. PMID: 32221012Free PMC Article
Patients Resistant Against PSMA-Targeting α-Radiation Therapy Often Harbor Mutations in DNA Damage-Repair-Associated Genes.
Kratochwil C, Giesel FL, Heussel CP, Kazdal D, Endris V, Nientiedt C, Bruchertseifer F, Kippenberger M, Rathke H, Leichsenring J, Hohenfellner M, Morgenstern A, Haberkorn U, Duensing S, Stenzinger A
J Nucl Med 2020 May;61(5):683-688. Epub 2019 Oct 10 doi: 10.2967/jnumed.119.234559. PMID: 31601699
Microsatellite Instability and Promoter Hypermethylation of DNA repair genes in Hematologic Malignancies: a forthcoming direction toward diagnostics.
Bhattacharya P, Patel TN
Hematology 2018 Mar;23(2):77-82. Epub 2017 Jul 20 doi: 10.1080/10245332.2017.1354428. PMID: 28728506
Prevalence of alterations in DNA mismatch repair genes in patients with young-onset colorectal cancer.
Limburg PJ, Harmsen WS, Chen HH, Gallinger S, Haile RW, Baron JA, Casey G, Woods MO, Thibodeau SN, Lindor NM
Clin Gastroenterol Hepatol 2011 Jun;9(6):497-502. Epub 2010 Nov 5 doi: 10.1016/j.cgh.2010.10.021. PMID: 21056691Free PMC Article

Prognosis

Clinical and biological landscape of constitutional mismatch-repair deficiency syndrome: an International Replication Repair Deficiency Consortium cohort study.
Ercan AB, Aronson M, Fernandez NR, Chang Y, Levine A, Liu ZA, Negm L, Edwards M, Bianchi V, Stengs L, Chung J, Al-Battashi A, Reschke A, Lion A, Ahmad A, Lassaletta A, Reddy AT, Al-Darraji AF, Shah AC, Van Damme A, Bendel A, Rashid A, Margol AS, Kelly BL, Pencheva B, Heald B, Lemieux-Anglin B, Crooks B, Koschmann C, Gilpin C, Porter CC, Gass D, Samuel D, Ziegler DS, Blumenthal DT, Kuo DJ, Hamideh D, Basel D, Khuong-Quang DA, Stearns D, Opocher E, Carceller F, Baris Feldman H, Toledano H, Winer I, Scheers I, Fedorakova I, Su JM, Vengoechea J, Sterba J, Knipstein J, Hansford JR, Gonzales-Santos JR, Bhatia K, Bielamowicz KJ, Minhas K, Nichols KE, Cole KA, Penney L, Hjort MA, Sabel M, Gil-da-Costa MJ, Murray MJ, Miller M, Blundell ML, Massimino M, Al-Hussaini M, Al-Jadiry MF, Comito MA, Osborn M, Link MP, Zapotocky M, Ghalibafian M, Shaheen N, Mushtaq N, Waespe N, Hijiya N, Fuentes-Bolanos N, Ahmad O, Chamdine O, Roy P, Pichurin PN, Nyman P, Pearlman R, Auer RC, Sukumaran RK, Kebudi R, Dvir R, Raphael R, Elhasid R, McGee RB, Chami R, Noss R, Tanaka R, Raskin S, Sen S, Lindhorst S, Perreault S, Caspi S, Riaz S, Constantini S, Albert S, Chaleff S, Bielack S, Chiaravalli S, Cramer SL, Roy S, Cahn S, Penna S, Hamid SA, Ghafoor T, Imam U, Larouche V, Magimairajan Issai V, Foulkes WD, Lee YY, Nathan PC, Maruvka YE, Greer MC, Durno C, Shlien A, Ertl-Wagner B, Villani A, Malkin D, Hawkins C, Bouffet E, Das A, Tabori U
Lancet Oncol 2024 May;25(5):668-682. Epub 2024 Mar 26 doi: 10.1016/S1470-2045(24)00026-3. PMID: 38552658
Novel MSH6 mutation predicted metastasis in eyelid and periocular squamous cell carcinoma.
Luo Y, Rao Y, Gu X, Chai P, Yang Y, Lin J, Xu X, Jia R, Xu S
J Eur Acad Dermatol Venereol 2022 Dec;36(12):2331-2342. Epub 2022 Aug 23 doi: 10.1111/jdv.18454. PMID: 35855666
Identification of SNPs in hMSH3/MSH6 interaction domain affecting the structure and function of MSH2 protein.
Singh S, Sharma S, Baranwal M
Biotechnol Appl Biochem 2022 Dec;69(6):2454-2465. Epub 2021 Dec 15 doi: 10.1002/bab.2295. PMID: 34837403
Prevalence and spectrum of DNA mismatch repair gene variation in the general Chinese population.
Zhang L, Qin Z, Huang T, Tam B, Ruan Y, Guo M, Wu X, Li J, Zhao B, Chian JS, Wang X, Wang L, Wang SM
J Med Genet 2022 Jul;59(7):652-661. Epub 2021 Jun 25 doi: 10.1136/jmedgenet-2021-107886. PMID: 34172528Free PMC Article
Frequency of Germline Mutations in 25 Cancer Susceptibility Genes in a Sequential Series of Patients With Breast Cancer.
Tung N, Lin NU, Kidd J, Allen BA, Singh N, Wenstrup RJ, Hartman AR, Winer EP, Garber JE
J Clin Oncol 2016 May 1;34(13):1460-8. Epub 2016 Mar 14 doi: 10.1200/JCO.2015.65.0747. PMID: 26976419Free PMC Article

Clinical prediction guides

Novel MSH6 mutation predicted metastasis in eyelid and periocular squamous cell carcinoma.
Luo Y, Rao Y, Gu X, Chai P, Yang Y, Lin J, Xu X, Jia R, Xu S
J Eur Acad Dermatol Venereol 2022 Dec;36(12):2331-2342. Epub 2022 Aug 23 doi: 10.1111/jdv.18454. PMID: 35855666
Low BRCA1 and BRCA2 Germline Mutation Rates in a French-Canadian Population with a Diagnosis of Epithelial Tubo-Ovarian Carcinoma.
Bernard J, Mehros W, Gregoire J, Douville P, Renaud MC, Sebastianelli A, Langlais EL, Plante M
J Obstet Gynaecol Can 2022 Oct;44(10):1047-1053. Epub 2022 Jun 30 doi: 10.1016/j.jogc.2022.06.005. PMID: 35779836
Prevalence and spectrum of DNA mismatch repair gene variation in the general Chinese population.
Zhang L, Qin Z, Huang T, Tam B, Ruan Y, Guo M, Wu X, Li J, Zhao B, Chian JS, Wang X, Wang L, Wang SM
J Med Genet 2022 Jul;59(7):652-661. Epub 2021 Jun 25 doi: 10.1136/jmedgenet-2021-107886. PMID: 34172528Free PMC Article
Low folate concentration impacts mismatch repair deficiency in neural tube defects.
Li H, Wang X, Zhao H, Wang F, Bao Y, Guo J, Chang S, Wu L, Cheng H, Chen S, Zou J, Cui X, Niswander L, Finnell RH, Wang H, Zhang T
Epigenomics 2020 Jan;12(1):5-18. Epub 2019 Nov 26 doi: 10.2217/epi-2019-0279. PMID: 31769301
Frequency of Germline Mutations in 25 Cancer Susceptibility Genes in a Sequential Series of Patients With Breast Cancer.
Tung N, Lin NU, Kidd J, Allen BA, Singh N, Wenstrup RJ, Hartman AR, Winer EP, Garber JE
J Clin Oncol 2016 May 1;34(13):1460-8. Epub 2016 Mar 14 doi: 10.1200/JCO.2015.65.0747. PMID: 26976419Free PMC Article

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