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    GENE:

    MSH2 (MutS Homolog 2)

    i
    Other names: MSH2, MutS Homolog 2, HMSH2, MutS (E. Coli) Homolog 2, MutS Homolog 2, Nonpolyposis Type 1, DNA Mismatch Repair Protein Msh2, MutS Protein Homolog 2, HNPCC1, HNPCC, LCFS2, COCA1, FCC1
    2d
    A novel lynch syndrome kindred with hereditary adrenal cortical carcinoma. (PubMed, Cancer Genet)
    A review of the literature identifies an association between germline MSH2 mutations and ACC, suggesting a potential biological basis for carcinogenesis. This case highlights the importance of ACC screening for patients with Lynch Syndrome and a family history of adrenal cortical carcinoma due to the high mortality from this malignancy. This case also highlights the importance of separate germline and somatic testing for patients with a concerning personal or family history of cancers.
    Journal • PD(L)-1 Biomarker • IO biomarker
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    MSH2 (MutS Homolog 2)
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    MSH2 mutation • MSH2 deletion
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    Keytruda (pembrolizumab)
    2d
    Multi-ethnic heterozygote frequencies of cancer susceptibility genes to inform counseling of reproductive risk. (PubMed, Genet Med)
    Heterozygote frequency estimates for AD CPGs that cause AR disease provides information to facilitate discussions regarding reproductive risk. Future studies are needed to assess whether utilization of these data will influence couples' reproductive risk planning.
    Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • SDHD (Succinate Dehydrogenase Complex Subunit D) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)
    3d
    Recurrent GRHL fusions in a subset of sebaceoma: microscopic and molecular characterisation of eight cases. (PubMed, Histopathology)
    In conclusion, we report recurrent fusions of the GRHL genes in a distinctive subset of sebaceomas harbouring infundibulocystic differentiation, a frequent organoid growth pattern and lack of mismatch repair deficiency.
    Journal
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    AR (Androgen receptor) • BCL6 (B-cell CLL/lymphoma 6) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • BCOR (BCL6 Corepressor) • TP63 (Tumor protein 63)
    |
    AR expression • MSH6 expression
    4d
    A novel mouse model recapitulating the MMR-defective SCLC subtype uncovers an actionable sensitivity to immune checkpoint blockade. (PubMed, J Cancer Res Clin Oncol)
    We propose a novel RPM mouse model as a suitable system to mimic MMR-defective SCLC and tumors with high TMB. We provide in vivo evidence that Msh2 deficiency enhances ICI sensitivity. These findings could contribute to stratifying SCLC patients to immunotherapy, thereby improving treatment outcomes.
    Preclinical • Journal • Checkpoint inhibition • Tumor mutational burden • IO biomarker • Checkpoint block
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    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • RB1 (RB Transcriptional Corepressor 1) • MSH2 (MutS Homolog 2)
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    TMB-H
    5d
    MSH2-Mutated Lynch Syndrome With 9 Synchronous Colon and Rectum Adenocarcinomas: An Extremely Rare Case Report. (PubMed, Int J Surg Pathol)
    Additionally, the report explores various aspects of having synchronous colorectal cancers. More studies are needed to clarify the clinicopathologic and molecular landscape of these rare tumors and identify the best management and treatment strategies for these patients.
    Journal
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    MSH2 (MutS Homolog 2)
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    MSH2 mutation
    6d
    The impact of preoperative treatment on mismatch repair protein and HER2 expression in colorectal cancer: an analysis of paired samples. (PubMed, BMC Cancer)
    PT is associated with a reduction in MMR expression, notably for the MSH2 protein, while it does not appear to influence HER2 expression.
    Retrospective data • Journal • Mismatch repair
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    HER-2 (Human epidermal growth factor receptor 2) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
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    MSI-H/dMMR • HER-2 overexpression • HER-2 expression • MSH6 expression
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    5-fluorouracil • capecitabine
    6d
    The genetic landscape of Lynch syndrome in the Israeli population. (PubMed, Fam Cancer)
    Though the 16 prevalent LS-associated DCVs were frequently detected in our cohort, none of them is frequently reported in the general population. These data should facilitate variant interpretation, spouse and cascade testing.
    Journal
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    MSH2 (MutS Homolog 2)
    6d
    Secondary findings in 443 exome sequencing data. (PubMed, Ann Hum Genet)
    Thirteen of above mentioned variants were classified as known pathogenic and four as expected pathogenic. The information collected in our study may lead to the prevention of severe morbidity and mortality and provides additional insight into the genetic background of the Serbian population.
    Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • PALB2 (Partner and localizer of BRCA2) • MSH2 (MutS Homolog 2) • MYH7 (Myosin Heavy Chain 7)
    6d
    Next-generation sequencing uncovers crucial mutated genes and potential therapeutic targets in ovarian cancer patients. (PubMed, Am J Transl Res)
    These findings provide novel insights into the genetic underpinnings of ovarian cancer in the Pakistani population and suggest potential targets for therapeutic intervention.
    Journal • Next-generation sequencing • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • CDK4 (Cyclin-dependent kinase 4) • MSH2 (MutS Homolog 2)
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    BRCA2 mutation • BRCA1 mutation • PTEN mutation • BRCA1 mutation + BRCA2 mutation • BRCA1 expression
    7d
    Advantages of next-generation sequencing (NGS) in the molecular classifi cation of endometrial carcinomas - our experience with 270 cases. (PubMed, Ceska Gynekol)
    In comparison with recommended diagnostic algorithms, NGS provides a more reliable classification of EC into particular molecular subgroups. Furthermore, NGS reveals the complex molecular genetic background in individual ECs, which is especially significant within ECs with no specific molecular profile. These data can serve as a springboard for the research of therapeutic programs committed to targeted therapy in this type of tumor.
    Journal • Next-generation sequencing • BRCA Biomarker
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    HER-2 (Human epidermal growth factor receptor 2) • 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) • POLE (DNA Polymerase Epsilon) • 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) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • POLD1 (DNA Polymerase Delta 1)
    |
    TP53 mutation • PIK3CA mutation • PTEN mutation • POLE mutation
    8d
    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
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    MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • EPCAM (Epithelial cell adhesion molecule)
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    MSH2 mutation • PMS2 mutation • MSH6 deletion
    8d
    Germline mismatch repair gene mutations in children with tumors: a case series from two centers. (PubMed, Transl Pediatr)
    A better diagnostic approach is to perform genetic testing to rule out the risk as early as possible when a newborn presents with cafe-au-lait spots, which are a typical feature of hereditary syndromes. Therefore, it is important to use germline genetic testing, combined with clinical phenotypic observation, to establish a diagnosis of a cancer susceptibility syndrome caused by an MMR gene mutation.
    Journal • Mismatch repair
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    NF1 (Neurofibromin 1) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
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    MSH6 mutation • MSH2 mutation • MLH1 mutation
    8d
    Founder pathogenic variants in colorectal neoplasia susceptibility genes in Ashkenazi Jews undergoing colonoscopy. (PubMed, BJC Rep)
    Overall, we found that 10 to 15% of Ashkenazi Jewish persons undergoing colonoscopy harbor variants of interest in colorectal and/or polyposis predisposition. This includes pathogenic variants in MSH6, which is associated with colorectal cancer but not with polyposis. We identified no pathogenic variants in more recently discovered polyposis predisposition genes (POLE, POLD1 or NTHL1), rendering the presence of such founder variants rare.
    Journal
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    MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • POLD1 (DNA Polymerase Delta 1)
    8d
    Characteristics of Cancer in Subjects Carrying Lynch Syndrome-Associated Gene Variants in Taiwanese Population: A Hospital-Based Study in Taiwan. (PubMed, Cancers (Basel))
    The apparent under diagnosis of LS highlights the urgent need for enhanced surveillance and genetic counseling in this demographic. Our findings suggest that adjustments in the current screening protocols may be warranted to better identify and manage at-risk individuals.
    Journal
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    MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
    9d
    Genomic alterations associated with early-stage disease and early recurrence in patients with colorectal cancer. (PubMed, Oncologist)
    Early-stage CRC patients can have distinct genomic profiles and CGP in this population can help expand access to targeted therapies.
    Journal • Tumor mutational burden • BRCA Biomarker • MSi-H Biomarker
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    BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • RNF43 (Ring Finger Protein 43)
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    BRAF V600E • MSI-H/dMMR • BRAF V600 • RNF43 mutation
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    FoundationOne® CDx
    11d
    Pembrolizumab Before Surgery for the Treatment of Mismatch Repair Deficient Locally Advanced Solid Cancers (clinicaltrials.gov)
    P2, N=35, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed
    Trial completion
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    MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
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    MSI-H/dMMR
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    Keytruda (pembrolizumab)
    12d
    Radiation and TSR-042 (Dostarlimab) in People With Endometrial Cancer After They Receive Surgery (clinicaltrials.gov)
    P2, N=62, Recruiting, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Recruiting | N=31 --> 62 | Trial completion date: Feb 2025 --> Feb 2026 | Trial primary completion date: Feb 2025 --> Feb 2026
    Enrollment open • Enrollment change • Trial completion date • Trial primary completion date • Checkpoint inhibition • Mismatch repair • Surgery • Checkpoint block • Metastases
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    MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
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    MSI-H/dMMR • POLE mutation
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    Jemperli (dostarlimab-gxly)
    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
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    BRAF (B-raf proto-oncogene) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
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    BRAF mutation • MSH2 mutation • MLH1 mutation • PMS2 mutation
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    NOUS-209
    13d
    A Phase 1/2 Study to Evaluate the Safety and Efficacy of MK-2870 Monotherapy or in Combination With Other Anticancer Agents in Gastrointestinal Cancers (ChiCTR2400089007)
    P2, N=130, Not yet recruiting, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; Union Hospital, Tongji Medical College, Huazhong University of
    New P2 trial • Combination therapy
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    MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • BRCA (Breast cancer early onset) • CD4 (CD4 Molecule)
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    MSI-H/dMMR • BRCA mutation • MSH6 expression
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    FoundationOne® CDx
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    5-fluorouracil • sacituzumab tirumotecan (MK-2870)
    16d
    A Phase 2 Study of Mirvetuximab Soravtansine (IMGN853) and Pembrolizumab in Endometrial Cancer (EC) (clinicaltrials.gov)
    P2, N=18, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Aug 2028 --> May 2027 | Trial primary completion date: Aug 2025 --> Jun 2024
    Trial completion date • Trial primary completion date • Combination therapy
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    FOLR1 ( Folate receptor alpha ) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
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    MSH6 expression
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    Keytruda (pembrolizumab) • Elahere (mirvetuximab soravtansine-gynx)
    16d
    Fecal Microbiota Transplant and Re-introduction of Anti-PD-1 Therapy (Pembrolizumab or Nivolumab) for the Treatment of Metastatic Colorectal Cancer in Anti-PD-1 Non-responders (clinicaltrials.gov)
    P2, N=15, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025
    Trial completion date • Trial primary completion date • Metastases
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    MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CEACAM5 (CEA Cell Adhesion Molecule 5)
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    MSI-H/dMMR
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    Keytruda (pembrolizumab) • Opdivo (nivolumab)
    16d
    Association Between the Protein Expressions of MutS Homologs and Villin and the Clinicopathological Characteristics in 310 Colon Cancer Patients (PubMed, Sichuan Da Xue Xue Bao Yi Xue Ban)
    The expressions of MSH2, MSH6, and villin are closely correlated with the pathological features of colon cancer patients. Evaluating the expression of the three proteins may assist in the clinical diagnosis, treatment, and prognosis evaluation of colon cancer.
    Journal
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    MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
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    MSH6 expression
    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
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    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)
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    BRCA2 mutation • BRCA1 mutation • PALB2 mutation • CDKN2A mutation • MLH1 mutation • PMS2 mutation • BRCA mutation
    17d
    High risk of multiple gastric cancers in Japanese individuals with Lynch syndrome. (PubMed, Ann Gastroenterol Surg)
    Notably, the cumulative risk of individuals with LS developing metachronous and/or synchronous GCs at 0, 10 and 20 y after initial diagnosis of GC was 26.7%, 40.7%, and 59.4%, respectively. Due to a higher risk of developing multiple GCs, intensive surveillance might be especially recommended for Japanese individuals with LS associated initial GC.
    Journal
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    MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
    19d
    Genetic and clinical characteristics of genetic tumor syndromes in the central nervous system cancers: Implications for clinical practice. (PubMed, iScience)
    The top five GTS in CNS tumors showed high genetic heterogeneity GTS analysis reclassifies CNS tumors as "NEC." 53.88% of patients diagnosed with GTS harbor potential precision oncology therapy target mutations. The results of our study deepen our understanding of CNS tumors, provide a reference direction for the future design of clinical trials, and further expect to improve disease entire process management in CNS tumors.
    Journal • BRCA Biomarker
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    TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • NF1 (Neurofibromin 1) • MSH2 (MutS Homolog 2)
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    TP53 mutation • NF1 mutation • MSH2 mutation
    1m
    Intraoperative rapid immunohistochemistry of microsatellite instability using non-contact alternating current electric field mixing. (PubMed, Gen Thorac Cardiovasc Surg)
    Rapid MMR-IHC could potentially serve as a clinical tool for intraoperative determination of tumor MSI/dMMR status. AC-mixing technology will contribute to improving pathological diagnostic capability through the development of an original and innovative rapid IHC.
    Journal • Microsatellite instability • MSi-H Biomarker • IO biomarker
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    MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
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    MSI-H/dMMR
    1m
    A new subtype of Lynch syndrome associated with MSH2 c.354T>A (p. Y118*) identified in a Chinese family: case report and literature review. (PubMed, Front Genet)
    This study provides evidence that the MSH2 nonsense mutation c.354T>A is a highly likely pathogenic mutation and is responsible for typical LS-associated endometrial carcinoma. It emphasizes the importance of genetic counseling for proband family members to facilitate early diagnosis of LS-related carcinoma.
    Review • Journal • MSi-H Biomarker
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    MSI (Microsatellite instability) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
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    MSI-H/dMMR • MSH2 mutation • MSH2 negative + MSH6 negative • MSH6 expression
    1m
    Germline testing of Iranian families suspected of Lynch syndrome: molecular characterization and current surveillance of families with pathogenic variants in MSH2, MSH6, and PMS2. (PubMed, Eur J Cancer Prev)
    Collecting blood samples at patients' convenience is a possible strategy to reduce the cost of identifying Lynch syndrome through cascade testing. The genetic analysis of patients for inherited cancers would optimize the current management of Lynch syndrome in Iran by omitting noncarriers from surveillance programs.
    Journal
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    MSI (Microsatellite instability) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • PMS1 (PMS1 protein homolog 1)
    1m
    Anticipation in families with MLH1-associated Lynch syndrome. (PubMed, Cancer)
    The current results demonstrated evidence in support of anticipation in families with MLH1-associated LS across all statistical models. Mutational effects on Mlh1 activity influenced the hazard for CRC/EC. Screening based on the youngest age of cancer diagnosis in MLH1-LS families is recommended.
    Journal
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    MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • EPCAM (Epithelial cell adhesion molecule)
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    MLH1 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
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    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
    The Cancer of the Pancreas Screening-5 CAPS5)Study (clinicaltrials.gov)
    P3, N=9000, Recruiting, Johns Hopkins University | Trial primary completion date: Oct 2024 --> Oct 2025
    Trial primary completion date
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSH2 (MutS Homolog 2) • PRSS1 (Serine Protease 1) • CA 19-9 (Cancer antigen 19-9) • CTRC (Chymotrypsin C)
    |
    BRCA1 mutation • PALB2 mutation
    1m
    Immunohistochemistry staining for DNA mismatch repair proteins in endoscopic biopsies and the corresponding surgical specimen in colorectal cancer. (PubMed, Rev Esp Enferm Dig)
    The correlation with results from the surgical specimen was notably high and discrepancies were primarily as a result of intratumoral heterogeneity within the same sample. The features of MMR protein loss in endoscopic biopsies can provide clinicians with valuable information for specific therapeutic approaches and genetic counseling.
    Journal • Mismatch repair • Biopsy
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    MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
    1m
    Oxaliplatin, Leucovorin Calcium, and Fluorouracil With or Without Bevacizumab in Treating Patients Who Have Undergone Surgery for Stage II Colon Cancer (clinicaltrials.gov)
    P3, N=3610, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Dec 2024 | Trial primary completion date: Sep 2024 --> Dec 2024
    Trial completion date • Trial primary completion date • Surgery
    |
    MSI (Microsatellite instability) • MSH2 (MutS Homolog 2)
    |
    Avastin (bevacizumab) • oxaliplatin • leucovorin calcium • fluorouracil topical
    1m
    Association of glutaminase expression with immune-suppressive tumor microenvironment, clinicopathologic features, and clinical outcomes in endometrial cancer. (PubMed, Int J Gynecol Cancer)
    Our findings indicate that increased glutaminase expression is associated with an immune-suppressive tumor microenvironment, poor clinicopathologic features, and worse long-term outcomes in patients with endometrial cancer.
    Clinical data • Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • ER (Estrogen receptor) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • CD68 (CD68 Molecule) • FOXP3 (Forkhead Box P3) • GLS1 (Glutaminase)
    |
    MYC expression
    1m
    DNA polymerase theta-mediated DNA repair is a functional dependency and therapeutic vulnerability in DNMT3A deficient leukemia cells. (PubMed, bioRxiv)
    Polθ inhibitors enhanced the anti-leukemic effects of mainstream drugs such as FLT3 kinase inhibitor quizartinib, cytarabine and etoposide in vitro and in mice with FLT3(ITD);DNMT3Amut leukemia. Altogether, Polθ is an attractive target in DNMT3Amut hematological malignancies.
    Journal • PARP Biomarker
    |
    FLT3 (Fms-related tyrosine kinase 3) • DNMT3A (DNA methyltransferase 1) • MSH2 (MutS Homolog 2) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • MSH3 (MutS Homolog 3)
    |
    DNMT3A mutation
    |
    cytarabine • etoposide IV • Vanflyta (quizartinib)
    1m
    Case report: Germline CHEK2 mutation is associated with a giant cell glioblastoma. (PubMed, Front Oncol)
    Additional mutations detected in the tumor included TP53, PTEN, and a PTPRZ1-MET fusion. This represents the first reported case of a CHEK2 germline mutation in giant cell glioblastoma, further supporting the significance of impaired DNA repair mechanisms in the development of this disease.
    Journal
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    TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • MSH2 (MutS Homolog 2) • CHEK2 (Checkpoint kinase 2) • PTPRZ1 (Protein Tyrosine Phosphatase Receptor Type Z1)
    |
    TP53 mutation • PTEN mutation • CHEK2 mutation • MSH2 mutation • MET fusion
    1m
    Durvalumab for MSI-H or POLE Mutated Metastatic Colorectal Cancer (clinicaltrials.gov)
    P2, N=33, Completed, Asan Medical Center | Active, not recruiting --> Completed
    Trial completion • Mismatch repair • Tumor mutational burden • Metastases
    |
    POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
    |
    MSI-H/dMMR • POLE mutation
    |
    Imfinzi (durvalumab) • oxaliplatin • irinotecan
    1m
    Comparative sequencing study of mismatch repair and homology-directed repair genes in endometrial cancer and breast cancer patients from Kazakhstan. (PubMed, Int J Cancer)
    One patient who developed breast cancer first and endometrial cancer later carried a novel frameshift variant in MSH6. Our results indicate that MMR and HDR gene variants with predicted pathogenicity occur at substantial frequencies in both breast and endometrial cancer patients from the Kazakh population.
    Journal • Mismatch repair
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • BARD1 (BRCA1 Associated RING Domain 1) • MUTYH (MutY homolog) • FANCM (FA Complementation Group M) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)
    1m
    Association between microsatellite instability status, clinicopathological features and mitochondrial DNA amplification in patients with colorectal cancer. (PubMed, Oncol Lett)
    Furthermore, the number of mitochondrial DNA was significantly amplified in the MSI-H group. In conclusion, the present study demonstrated that the combined detection of PD-L1 and MSI in patients with CRC can provide more accurate and effective guidance for personalized treatment.
    Journal • Microsatellite instability • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • BRAF (B-raf proto-oncogene) • MSI (Microsatellite instability) • PD-1 (Programmed cell death 1) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
    |
    PD-L1 expression • BRAF V600E • MSI-H/dMMR • BRAF V600
    1m
    The molecular genetics of adrenal cushing. (PubMed, Hormones (Athens))
    Syndromic PBMAH may be due to germline pathogenic variants in MEN1, APC, or FH, causing type 1 multiple endocrine neoplasia, familial adenomatous polyposis, or hereditary leiomyomatosis-kidney cancer syndrome, respectively. PRKAR1A germline pathogenic variants are the main alteration causing PPNAD (isolated or part of Carney complex).
    Review • Journal • BRCA Biomarker
    |
    TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • NF1 (Neurofibromin 1) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • IGF2 (Insulin-like growth factor 2) • GNAS (GNAS Complex Locus) • PRKACA (Protein Kinase CAMP-Activated Catalytic Subunit Alpha) • PRKAR1A (Protein Kinase CAMP-Dependent Type I Regulatory Subunit Alpha) • CDKN1C (Cyclin Dependent Kinase Inhibitor 1C) • PRKACB (Protein Kinase CAMP-Activated Catalytic Subunit Beta) • ZNRF3 (Zinc And Ring Finger 3)
    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
    S2107: Testing the Addition of Nivolumab to Standard Treatment for Patients With Metastatic or Unresectable Colorectal Cancer That Have a BRAF Mutation (clinicaltrials.gov)
    P2, N=84, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2025 --> Feb 2026 | Trial primary completion date: Aug 2024 --> Feb 2026
    Trial completion date • Trial primary completion date • Metastases
    |
    BRAF (B-raf proto-oncogene) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
    |
    BRAF V600E • BRAF V600
    |
    Opdivo (nivolumab) • Erbitux (cetuximab) • Braftovi (encorafenib) • ABP 206 (nivolumab biosimilar)