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    BIOMARKER:

    PMS2 mutation

    i
    Other names: PMS2, PMS1 Homolog 2, Mismatch Repair System Component, PMS1 Homolog 2, Mismatch Repair Protein, Mismatch Repair Endonuclease PMS2, DNA Mismatch Repair Protein PMS2, PMS1 Protein Homolog 2, PMSL2, PMS2 Postmeiotic Segregation Increased 2, Postmeiotic Segregation Increased 2 Nirs Variant 6, PMS2 Postmeiotic Segregation Increased 2, HNPCC4, PMS2CL, MLH4
    Entrez ID:
    5395
    Related biomarkers:
    Expression
    Mutation
    CNA
    Others
    7d
    The guidelines for clinical practice for carriers of germline mutations in the Lynch syndrome predisposition genes MLH1, MSH2, MSH6, PMS2 and large deletions of EPCAM (4.2024). (PubMed, Klin Onkol)
    The drafting of the guidelines was organized by the Oncogenetics Working Group of the Society for Medical Genetics and Genomics of J. E. Purkyně Czech Medical Society, in cooperation with representatives of oncology, oncogynecology, and gastroenterology. The guidelines are based on the current recommendations of the National Comprehensive Cancer Network (NCCN), European Society of Medical Oncology (ESMO) and take into account the capacity of the Czech healthcare system.
    Clinical guideline • Journal
    |
    MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • EPCAM (Epithelial cell adhesion molecule)
    |
    MSH2 mutation • PMS2 mutation • MSH6 deletion
    12d
    Cancer Preventive Vaccine Nous-209 for Lynch Syndrome Patients (clinicaltrials.gov)
    P1/2, N=60, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    BRAF (B-raf proto-oncogene) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
    |
    BRAF mutation • MSH2 mutation • MLH1 mutation • PMS2 mutation
    |
    NOUS-209
    17d
    PancreasScan: Pancreatic Cancer Screening for At-risk Individuals (clinicaltrials.gov)
    P=N/A, N=1395, Recruiting, Beth Israel Deaconess Medical Center | N=500 --> 1395 | Trial completion date: Mar 2028 --> Dec 2032 | Trial primary completion date: Mar 2027 --> Dec 2032
    Enrollment change • Trial completion date • Trial primary completion date
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • BRCA (Breast cancer early onset) • EPCAM (Epithelial cell adhesion molecule) • PRSS1 (Serine Protease 1)
    |
    BRCA2 mutation • BRCA1 mutation • PALB2 mutation • CDKN2A mutation • MLH1 mutation • PMS2 mutation • BRCA mutation
    1m
    Cohort Study of Pancreatic Cancer Risk (clinicaltrials.gov)
    P=N/A, N=419, Active, not recruiting, Mayo Clinic | N=2000 --> 419
    Enrollment change
    |
    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • APC (APC Regulator Of WNT Signaling Pathway) • EPCAM (Epithelial cell adhesion molecule)
    |
    TP53 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • APC mutation • MSH2 mutation • PMS2 mutation
    1m
    Analyzing the mutational landscape of prostate cancer susceptibility genes through next-generation sequencing (NGS). (PubMed, Am J Transl Res)
    This comprehensive analysis emphasizes the critical roles of BRCA1, BRCA2, TP53, and PMS2 in prostate cancer pathogenesis and highlights the importance of population-specific genetic screening.
    Journal • Next-generation sequencing • BRCA Biomarker
    |
    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PMS2 (PMS1 protein homolog 2)
    |
    TP53 mutation • BRCA2 mutation • BRCA1 mutation • BRCA1 mutation + BRCA2 mutation • PMS2 mutation • TP53 expression • BRCA1 expression • BRCA2 expression
    1m
    MSH6-proficient crypt foci in MSH6 constitutional mismatch repair deficiency: reversion of a frameshifted coding microsatellite to its wild-type sequence. (PubMed, Fam Cancer)
    In conclusion, our study documents distinct MMRp-crypts in MSH6-CMMRD, a phenomenon in keeping with MSH6 being a frequent target of MSI-H due to its coding microsatellite and suggesting that MSH6-CMMRD can potentially serve as a unique model system to further our understanding of MSH6's role in MSI-H tumor formation and evolution. Our findings also bear diagnostic implications; when using MMR immunohistochemistry as an ancillary tool in detecting CMMRD, awareness of these MMRp crypts can help avoid diagnostic pitfalls.
    Journal • Mismatch repair • MSi-H Biomarker
    |
    MSI (Microsatellite instability) • MSH6 (MutS homolog 6) • PMS2 (PMS1 protein homolog 2) • APC (APC Regulator Of WNT Signaling Pathway)
    |
    MSI-H/dMMR • APC mutation • PMS2 mutation
    2ms
    PROGRESS: Prostate Cancer Genetic Risk Evaluation and Screening Study (clinicaltrials.gov)
    P=N/A, N=400, Recruiting, Massachusetts General Hospital | N=200 --> 400
    Enrollment change
    |
    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • EPCAM (Epithelial cell adhesion molecule) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • GEN1 (GEN1 Holliday junction 5' flap endonuclease) • HOXB13 (Homeobox B13)
    |
    CHEK2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • PMS2 mutation • NBN mutation
    2ms
    CHARACTERIZATION OF GENETIC ANCESTRY IN WOMEN DIAGNOSED WITH TRIPLE NEGATIVE BREAST AND HIGH-GRADE SEROSOUS OVARIAN CANCER, HEREDITARY/SPORADIC: IMPLEMENTATION OF A DIAGNOSTIC PANEL (IGCS 2024)
    116 patients with a confirmatory primary diagnosis of TNBC (N= 75) and HGSOC (N= 41) were included. A higher Native American ancestry (NAM) proportion was observed in the hereditary group across the cohort (58% vs 45.2%). Among TNBC patients, hereditary cases exhibited a higher NAM ancestry mean (0.50 (SD, 0.14)).
    Clinical • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • PMS2 (PMS1 protein homolog 2) • CDH1 (Cadherin 1)
    |
    BRCA2 mutation • BRCA1 mutation • ATM mutation • PMS2 mutation • CDH1 mutation
    |
    TruSight Hereditary Cancer Panel
    2ms
    PMS2 mutation spectra in Norway and risk of cancer for carriers of pathogenic variants. (PubMed, Hered Cancer Clin Pract)
    After 15 years of genetic testing, 29 different class 4/5 variants have been detected in Norway. Almost half of Norwegian PMS2 carriers have the founder variant 989-1G > T. Penetrance of colorectal cancer in our cohort was moderate but variable, as 11.5% of those diagnosed were younger than 40 years.
    Journal
    |
    PMS2 (PMS1 protein homolog 2)
    |
    PMS2 mutation
    2ms
    Clinicopathological Characteristics and Outcomes of Colorectal Cancer With Heterogenous Staining of Mismatch Repair Protein. (PubMed, Dis Colon Rectum)
    Heterogenous mismatch repair protein staining in colorectal cancer exhibits distinct associations with tumor location, stage, microsatellite instability, BRAF mutation and prognosis. It is recommended to report MSH6 heterogeneity as it may indicate microsatellite instability-high. See Video Abstract.
    Journal • Mismatch repair • MSi-H Biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
    |
    KRAS mutation • MSI-H/dMMR • BRAF mutation • PMS2 mutation • MSH6 expression
    2ms
    Acolbifene Versus Low Dose Tamoxifen for the Prevention of Breast Cancer in Premenopausal Women at High Risk for Development of Breast Cancer (clinicaltrials.gov)
    P2, N=80, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting | Trial primary completion date: Sep 2026 --> Aug 2027
    Enrollment open • Trial primary completion date
    |
    TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • ATM (ATM serine/threonine kinase) • NF1 (Neurofibromin 1) • MSH6 (MutS homolog 6) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • AGR2 (Anterior gradient 2)
    |
    TP53 mutation • ATM mutation • PTEN mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • PMS2 mutation • BARD1 mutation • NBN mutation
    |
    tamoxifen • acolbifene
    2ms
    The clinical utility of next generation sequencing in endometrial cancer: focusing on molecular subtyping and lynch syndrome. (PubMed, Front Genet)
    Conducting germline mutation testing for MMR genes in all patients with endometrial carcinoma can effectively prevent instances of overlooked LS diagnoses. Nevertheless, the extensive expenses associated with NGS necessitate additional validation and investigation before its clinical implementation can be fully endorsed.
    Journal • Next-generation sequencing
    |
    TP53 (Tumor protein P53) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • EPCAM (Epithelial cell adhesion molecule)
    |
    TP53 mutation • MSH2 mutation • MLH1 mutation • PMS2 mutation
    2ms
    Gastric adenocarcinoma with intestinal progenitor cell differentiation: a morphologically underdiagnosed and more invasive distinctive type of gastric adenocarcinoma. (PubMed, Am J Cancer Res)
    Accurate identification of GAED is crucial in pathological practice, as it helps differentiate between GAED and conventional adenocarcinoma and aids in the evaluation of tumor malignancy. Furthermore, it is imperative to conduct a differential diagnosis that involves hepatoid adenocarcinoma, yolk sac tumor-like adenocarcinoma, and metastatic hepatocellular carcinoma.
    Journal
    |
    MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • GPC3 (Glypican 3) • MME (Membrane Metalloendopeptidase) • CDX2 (Caudal Type Homeobox 2) • SALL4 (Spalt Like Transcription Factor 4)
    |
    PMS2 mutation
    3ms
    Molecular substratification of endometrial carcinomas with no special molecular profile (NSMP) by using a limited NGS custom panel may facilitate effective patient selection for the PIK3CA-targeted therapy. (PubMed, Virchows Arch)
    Of those, 21% contain the PIK3CA mutation as a sole EC-associated oncogene mutation, while 79% harbor at least one more mutated gene. These findings may inform future healthcare planning and improve the effectiveness of EC patient selection for the PIK3CA-targeted therapy.
    Journal • Next-generation sequencing • BRCA Biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • PMS2 (PMS1 protein homolog 2) • BCOR (BCL6 Corepressor) • POLD1 (DNA Polymerase Delta 1)
    |
    KRAS mutation • PIK3CA mutation • PTEN mutation • ARID1A mutation • PMS2 mutation
    3ms
    The first case of Lynch syndrome associated penile cancer harboring a heterozygous PMS2 frameshift variant. (PubMed, Urol Int)
    These observations provided evidence suggesting that PSCC could be part of the LS spectrum.
    Journal • Tumor mutational burden • MSi-H Biomarker
    |
    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • PMS2 (PMS1 protein homolog 2)
    |
    TMB-H • MSI-H/dMMR • PMS2 mutation
    6ms
    Assessing Mismatch Repair Expression by Immunohistochemistry in Colorectal Adenocarcinoma -Insight from a Tertiary Care Centre. (PubMed, Gulf J Oncolog)
    In conclusion, our study provides valuable insights into the expression of mismatch repair in colorectal adenocarcinoma through immunohistochemistry analysis conducted at our tertiary care centre. These findings hold significant clinical implications, suggesting further testing for BRAF and MLH1 Promoter Hypermethylation to confirm possibility of Lynch syndrome.
    Journal • Mismatch repair
    |
    BRAF (B-raf proto-oncogene) • MSI (Microsatellite instability) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
    |
    BRAF mutation • MLH1 mutation • PMS2 mutation • MSH6 expression
    6ms
    Precision immuno-oncology approach for four malignant tumors in siblings with constitutional mismatch repair deficiency syndrome. (PubMed, NPJ Precis Oncol)
    Treatment involving immune checkpoint inhibitors significantly contributed to prolonged survival in both patients affected by lethal gliomas. The uniform hypermutation also allowed immune-directed treatment using nivolumab for the B-cell lymphoma, thereby limiting the intensive chemotherapy exposure in this young patient who remains at risk for subsequent malignancies.
    Journal • Mismatch repair • PD(L)-1 Biomarker • IO biomarker • Immuno-oncology
    |
    MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
    |
    MSH2 mutation • PMS2 mutation
    |
    Opdivo (nivolumab)
    7ms
    The Relationship of Microsatellite Instability with BRAF and p53 Mutations and Histopathological Parameters in Colorectal Adenocarcinoma. (PubMed, Ann Ital Chir)
    In colorectal adenocarcinoma, MSI and BRAF mutation are associated with parameters, indicating the host immune response and prognostic histopathological parameters, including tumor size and histological grade. The evaluation of MSI status and BRAF mutation can be particularly informative for predicting the prognosis and guiding the treatment management in poorly differentiated colorectal adenocarcinoma. Understanding the mechanisms of molecular carcinogenesis in colorectal carcinoma and organizing treatment algorithms based on molecular foundations will increase the success of the treatment.
    Journal • Microsatellite instability
    |
    BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
    |
    TP53 mutation • BRAF mutation • PMS2 mutation • BRAF mutation + TP53 mutation
    7ms
    In vitro data suggest a role for PMS2 Kozak sequence mutations in Lynch Syndrome risk. (PubMed, HGG Adv)
    Besides the c.1A>C variant, which is already known to be pathogenic, we implicate six additional variants as ACMG/AMP pathogenic supporting (PP) variants and classify ten as benign supporting (BP). In summary, we present a method developed for the classification of human PMS2 Kozak sequence variants that can contribute to the re-classification of VUSs identified in patients.
    Preclinical • Journal
    |
    PMS2 (PMS1 protein homolog 2)
    |
    PMS2 mutation
    7ms
    Cancer Preventive Vaccine Nous-209 for Lynch Syndrome Patients (clinicaltrials.gov)
    P1/2, N=60, Recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2025 --> Jul 2025 | Trial primary completion date: Mar 2025 --> Jul 2025
    Trial completion date • Trial primary completion date
    |
    BRAF (B-raf proto-oncogene) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
    |
    BRAF mutation • MSH2 mutation • MLH1 mutation • PMS2 mutation
    |
    NOUS-209
    7ms
    Acolbifene Versus Low Dose Tamoxifen for the Prevention of Breast Cancer in Premenopausal Women at High Risk for Development of Breast Cancer (clinicaltrials.gov)
    P2, N=80, Not yet recruiting, National Cancer Institute (NCI) | Phase classification: P2a --> P2 | Initiation date: Mar 2024 --> Oct 2024
    Phase classification • Trial initiation date
    |
    TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • ATM (ATM serine/threonine kinase) • NF1 (Neurofibromin 1) • MSH6 (MutS homolog 6) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • AGR2 (Anterior gradient 2)
    |
    TP53 mutation • ATM mutation • PTEN mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • PMS2 mutation • BARD1 mutation • NBN mutation
    |
    tamoxifen • acolbifene
    8ms
    Combination Chemotherapy With or Without Atezolizumab in Treating Patients With Stage III Colon Cancer and Deficient DNA Mismatch Repair (clinicaltrials.gov)
    P3, N=700, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Apr 2024 --> Apr 2025 | Trial primary completion date: Apr 2024 --> Apr 2025
    Trial completion date • Trial primary completion date • Mismatch repair • Tumor mutational burden
    |
    MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CD4 (CD4 Molecule)
    |
    MSI-H/dMMR • MSH2 mutation • MLH1 mutation • PMS2 mutation • MSH6 expression
    |
    Tecentriq (atezolizumab) • oxaliplatin • leucovorin calcium • fluorouracil topical
    8ms
    A Pancreatic Cancer Screening Study in Hereditary High Risk Individuals (clinicaltrials.gov)
    P=N/A, N=200, Recruiting, Nuvance Health | N=100 --> 200
    Enrollment change
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
    |
    BRCA1 mutation • ATM mutation • PALB2 mutation • CDKN2A mutation • MSH2 mutation • PMS2 mutation
    8ms
    Clinical and biological landscape of constitutional mismatch-repair deficiency syndrome: an International Replication Repair Deficiency Consortium cohort study. (PubMed, Lancet Oncol)
    The very high cancer burden and unique genomic landscape of CMMRD highlight the benefit of comprehensive assays in timely diagnosis and precision approaches toward surveillance and immunotherapy. These data will guide the clinical management of children and patients who survive into adulthood with CMMRD.
    Journal • Mismatch repair • IO biomarker
    |
    MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
    |
    MSH2 mutation • MLH1 mutation • PMS2 mutation
    8ms
    PancreasScan: Pancreatic Cancer Screening for At-risk Individuals (clinicaltrials.gov)
    P=N/A, N=500, Recruiting, Beth Israel Deaconess Medical Center | Trial completion date: Jul 2026 --> Mar 2028 | Trial primary completion date: Jul 2025 --> Mar 2027
    Trial completion date • Trial primary completion date
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • BRCA (Breast cancer early onset) • EPCAM (Epithelial cell adhesion molecule) • PRSS1 (Serine Protease 1)
    |
    BRCA2 mutation • BRCA1 mutation • PALB2 mutation • CDKN2A mutation • MLH1 mutation • PMS2 mutation • BRCA mutation
    8ms
    Biomarker characterization in endometrial cancer in Europe: first survey data analysis from 69 pathological academic and hospital labs. (PubMed, Pathologica)
    Other markers (mainly p53 followed by POLE and PTEN) are investigated in particular in Spain and Switzerland in a consistent number of cases. Guidelines consultation and standardization of laboratory procedures are efficient means for EC prognostic risk stratification and improving the quality of care.
    Journal
    |
    BRAF (B-raf proto-oncogene) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
    |
    TP53 mutation • BRAF mutation • BRAF V600 • PMS2 mutation
    8ms
    Cancer Preventive Vaccine Nous-209 for Lynch Syndrome Patients (clinicaltrials.gov)
    P1/2, N=60, Recruiting, National Cancer Institute (NCI) | N=45 --> 60 | Trial completion date: Jul 2025 --> Mar 2025 | Trial primary completion date: Jul 2025 --> Mar 2025
    Enrollment change • Trial completion date • Trial primary completion date
    |
    BRAF (B-raf proto-oncogene) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
    |
    BRAF mutation • MSH2 mutation • MLH1 mutation • PMS2 mutation
    |
    NOUS-209
    9ms
    A Phase IIa Randomized, Double-Blinded Clinical Trial of Naproxen or Aspirin for Cancer Immune Interception in Lynch Syndrome (clinicaltrials.gov)
    P2, N=40, Recruiting, M.D. Anderson Cancer Center | Phase classification: P2a --> P2
    Phase classification
    |
    MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
    |
    MSI-H/dMMR • MSH2 mutation • MLH1 mutation • PMS2 mutation
    |
    aspirin
    9ms
    Mainstream Model of Genetic Testing for Prostate Cancer at a Large Tertiary Cancer Centre. (PubMed, Clin Genitourin Cancer)
    We report on the real-world characteristics of prostate cancer patients who underwent mainstream germline genetic testing. Personal history and family history of cancer cannot reliably stratify patients for the presence of pathogenic germline variants.
    Journal • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PMS2 (PMS1 protein homolog 2) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • HOXB13 (Homeobox B13)
    |
    BRCA2 mutation • BRCA1 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • PMS2 mutation
    9ms
    GC 2nd Line Durvalumab(MEDI4736)/Tremelimumab Plus Paclitaxel Study (clinicaltrials.gov)
    P1/2, N=58, Completed, Asan Medical Center | Active, not recruiting --> Completed
    Trial completion
    |
    PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • POLD1 (DNA Polymerase Delta 1) • MSH3 (MutS Homolog 3) • PMS1 (PMS1 protein homolog 1) • POLD2 (DNA Polymerase Delta 2)
    |
    MSI-H/dMMR • MSH2 mutation • MLH1 mutation • PD-L1 amplification • POLD1 mutation • MSH3 mutation • PMS2 mutation • MLH3 mutation • PMS1 mutation • POLD2 mutation
    |
    Imfinzi (durvalumab) • paclitaxel • Imjudo (tremelimumab)
    9ms
    Correlation of PTEN Alterations with Immunohistochemistry in POLE-Mutated and Mismatch Repair-Deficient Endometrial Carcinoma (USCAP 2024)
    In summary, PTEN IHC expression was retained in the majority of PTEN- and POLE-mutated ECs with frequent missense mutations in codon 130. Some codon 130 mutations (e.g., R130Q) are known to be associated with protein stability. Nearly half of PTEN-mutated MMR-d ECs were associated with PTEN expression (retained, reduced or subclonal loss).
    Mismatch repair
    |
    MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • PMS2 (PMS1 protein homolog 2)
    |
    MSI-H/dMMR • PTEN mutation • POLE mutation • PTEN expression • PMS2 mutation
    |
    Oncomine™ Comprehensive Assay v3M
    9ms
    Endometrial Cancers with Low Level Microsatellite Instability: Classification Pitfalls and Practical Recommendations for Assigning Mismatch Repair Status by Next Generation Sequencing with MSIsensor and Ancillary Tests (USCAP 2024)
    MSIsensor scores as low as 3.5% may represent true MMRd in EC tested by NGS. Further testing for MMRd is advised for MSIsensor scores between 3% and 30%, particularly if there is low tumor content or associated high TMB. In this setting, MMR IHC may have superior sensitivity for detection of MMRd compared to DNA-based assays.
    Microsatellite instability • Tumor mutational burden • IO biomarker • Next-generation sequencing • Mismatch repair
    |
    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
    |
    TMB-H • POLE mutation • MSH6 mutation • MSH2 mutation • PMS2 mutation
    |
    Idylla™ MSI Test
    9ms
    Next-Generation Sequencing Experience of Colorectal Cancer at a Quebec Health Care Centre (USCAP 2024)
    Our study is concordant with larger CRC sequencing studies. Although, the main targetable mutations are covered by the Focus Panel, a considerable proportion of specimens had no identifiable mutations. As more treatments become available, more extensive panels are necessary.
    Next-generation sequencing
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • PMS2 (PMS1 protein homolog 2)
    |
    KRAS mutation • BRAF mutation • PIK3CA mutation • HER-2 mutation • APC mutation • PMS2 mutation
    |
    Illumina Focus Panel
    9ms
    Metagenomic Evaluation of the Gut Microbiome in Patients With Lynch Syndrome and Other Hereditary Colonic Polyposis Syndromes (clinicaltrials.gov)
    P=N/A, N=77, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Feb 2024 --> Feb 2025 | Trial primary completion date: Feb 2024 --> Feb 2025
    Trial completion date • Trial primary completion date
    |
    STK11 (Serine/threonine kinase 11) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • SMAD4 (SMAD family member 4) • APC (APC Regulator Of WNT Signaling Pathway) • EPCAM (Epithelial cell adhesion molecule) • BMPR1A (Bone Morphogenetic Protein Receptor Type 1A)
    |
    MSH2 mutation • MLH1 mutation • PMS2 mutation
    9ms
    Differential responses to immune checkpoint inhibitors are governed by diverse mismatch repair gene alterations. (PubMed, Clin Cancer Res)
    Patients with mutS co-loss experienced longer mOS in CRC and EC and better response to ICIs in CRC. Among all explored biomarkers, NAL was higher in mutS co-loss and may be a potential driving factor for the observed better outcomes. TMB did not reliably predict NAL.
    Journal • Checkpoint inhibition • Mismatch repair • Tumor mutational burden • IO biomarker
    |
    TMB (Tumor Mutational Burden) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
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    MSI-H/dMMR • PMS2 mutation
    10ms
    The new 2023 FIGO staging system for endometrial cancer: what is different from the previous 2009 FIGO staging system? (PubMed, J Gynecol Oncol)
    The 2023 staging system for EC subdivided stages I and II compared to the 2009 system. The 2023 system with molecular classification is a good predictor of survival.
    Journal
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    POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • PMS2 (PMS1 protein homolog 2)
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    TP53 mutation • POLE mutation • PMS2 mutation
    10ms
    Genotype-phenotype correlations in carriers of the PMS2 founder variant c.1831dup. (PubMed, Mol Genet Genomic Med)
    Our results suggest that the PMS2 c.1831dup PV represents a, probably ancient, founder mutation and is possibly associated with an earlier CRC diagnosis compared to other PMS2 PVs.
    Journal
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    PMS2 (PMS1 protein homolog 2)
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    PMS2 mutation
    10ms
    PD-L1 diffuse large B-cell lymphoma with extremely high mutational burden and microsatellite instability due to acquired PMS2 mutation. (PubMed, Cold Spring Harb Mol Case Stud)
    This report, while highlighting the extent of possible tumor heterogeneity across separate clonal expansions as well as possible syndromic B-cell neoplasia, supports the notion that, although rare, PD-L1 expression and associated states permissive of high mutational burden (such as mismatch repair gene loss of function/MSI) should be more routinely considered in DLBCLs. Appropriate testing may be predictive of outcome and inform the utility of targeted therapy in these genetically diverse and historically treatment-refractory malignancies.
    Journal • Tumor mutational burden • Microsatellite instability • PD(L)-1 Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • PMS2 (PMS1 protein homolog 2)
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    PD-L1 expression • TMB-H • PMS2 mutation
    11ms
    Cycling in Preventing Colorectal Cancer in Participants With Lynch Syndrome (clinicaltrials.gov)
    P=N/A, N=21, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | Trial completion date: Dec 2024 --> Jan 2024 | Trial primary completion date: Dec 2024 --> Jan 2024
    Trial completion • Trial completion date • Trial primary completion date
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    MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • EPCAM (Epithelial cell adhesion molecule)
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    MSI-H/dMMR • MSH2 mutation • MLH1 mutation • PMS2 mutation
    11ms
    Cycling in Preventing Colorectal Cancer in Participants With Lynch Syndrome (clinicaltrials.gov)
    P=N/A, N=21, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024
    Trial completion date • Trial primary completion date
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    MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • EPCAM (Epithelial cell adhesion molecule)
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    MSI-H/dMMR • MSH2 mutation • MLH1 mutation • PMS2 mutation
    12ms
    A multicohort phase 2 trial of ADT, docetaxel plus nivolumab in patients with de novo metastatic hormone-sensitive prostate cancer enriched for inflamed tumors and DNA damage repair defects. (ASCO-GU 2024)
    After January 2022, the addition of standard of care abiraterone/prednisone was allowed after 7 months of study treatment at investigator discretion. Clinical trial information: NCT04126070.PD-L1 Combined Positive Score (CPS) ≥ 1 and/or CD T cell density ≥ 200. Homozygous deletions and/or deleterious mutations in a DDR gene, including and not limited to BRCA2, ATM, CHECK2, BRCA1, PALB2, RAD51D, ATR, NBN, PMS2, GEN1, MLH1, MSH2, MSH6, RAD51C, MRE11A, BRIP1, FAM175A, and CDK12.
    P2 data • Clinical • PD(L)-1 Biomarker • BRCA Biomarker • IO biomarker • Metastases
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    PD-L1 (Programmed death ligand 1) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CD8 (cluster of differentiation 8) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CDK12 (Cyclin dependent kinase 12) • PMS2 (PMS1 protein homolog 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • ABRAXAS1 (Abraxas 1 BRCA1 A Complex Subunit 2) • GEN1 (GEN1 Holliday junction 5' flap endonuclease)
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    PD-L1 expression • ATM mutation • PALB2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • PMS2 mutation • MRE11A mutation • NBN mutation
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    OncoPanel™ Assay
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    Opdivo (nivolumab) • docetaxel • abiraterone acetate
    12ms
    Molecular and clinical characteristics of POLE/POLD1 alterations among patients with colorectal cancer. (ASCO-GI 2024)
    POLE/POLD1 mutations frequently co-exist with MSI-H disease in CRC. Patients with MSS-CRC harboring POLE/POLD1 mutations represent a smaller subgroup of CRC (~1%). The incidence of POLE/POLD1 somatic mutations was more common among patients with colon cancer than those with rectal cancer.
    Clinical • MSi-H Biomarker
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    MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • POLD1 (DNA Polymerase Delta 1)
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    MSI-H/dMMR • POLE mutation • MSH6 mutation • MSH2 mutation • MLH1 mutation • POLD1 mutation • PMS2 mutation • POLE mutation + POLD1 mutation