News - MSH2 mutation - LARVOL VERI

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

9 days ago

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

14d

Plasma ctDNA enables early detection of temozolomide resistance mutations in glioma. (PubMed, Neurooncol Adv)

Furthermore, plasma ctDNA detection of new MMR gene mutations not present in the initial tissue biopsy may provide an early indication of the development of chemotherapy resistance. Additional clinical validation in larger cohorts is needed.

14 days ago

Journal • Circulating tumor DNA

MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)

MSH2 mutation

TruSight Oncology 500 Assay

temozolomide

17d

Mitotic abnormalities precede microsatellite instability in lynch syndrome-associated colorectal tumourigenesis. (PubMed, EBioMedicine)

The results validate our previous findings from mice and highlight early mitotic abnormalities as an important contributor and precancerous marker of colorectal tumourigenesis in LS.

17 days ago

Journal • Microsatellite instability

MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)

MSH6 mutation • MSH2 mutation • MLH1 mutation

20d

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

20 days ago

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

23d

A Pancreatic Cancer Screening Study in Hereditary High Risk Individuals (clinicaltrials.gov)

P=N/A, N=200, Recruiting, Nuvance Health | N=100 --> 200

23 days ago

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

25d

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.

25 days ago

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

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

1 month ago

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

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

1 month ago

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

2ms

Identification of Genes with Rare Loss of Function Variants Associated with Aggressive Prostate Cancer and Survival. (PubMed, Eur Urol Oncol)

This study provides further support that rare pLOF variants in specific genes are likely to increase aggressive PrCa risk and may help define the panel of informative genes for screening and treatment considerations.

2 months ago

Journal • BRCA Biomarker

BRCA2 (Breast cancer 2, early onset) • MLH1 (MutL homolog 1) • MSH2 (MutS Homolog 2) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))

ATM mutation • MSH2 mutation • NBN mutation

2ms

Evaluation of a Multimodal Strategy for Early Diagnosis of Men at High Genetic Risk of Prostate Cancer (HRPCa-II) (clinicaltrials.gov)

P=N/A, N=880, Not yet recruiting, Assistance Publique - Hôpitaux de Paris | Trial completion date: Nov 2027 --> Jul 2029 | Trial primary completion date: Nov 2027 --> Jul 2029

2 months ago

Trial completion date • Trial primary completion date

TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • HOXB13 (Homeobox B13)

BRCA1 mutation • PTEN mutation • PALB2 mutation • BRIP1 mutation • MSH2 mutation • RAD51C mutation • RAD51D mutation • RAD50 mutation • BARD1 mutation • BLM mutation • MRE11A mutation • MLH3 mutation • NBN mutation

2ms

GC 2nd Line Durvalumab(MEDI4736)/Tremelimumab Plus Paclitaxel Study (clinicaltrials.gov)

P1/2, N=58, Completed, Asan Medical Center | Active, not recruiting --> Completed

2 months ago

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)

2ms

Determining MSI status of prostate and cholangiocellular carcinoma by genome wide NGS (DKK 2024)

MSI estimation using NGS is suitable as a quick screening tool. Since thresholds for MSI-H might differ enormously between entities, additional IHC testing is recommended at least in samples where VUS or pathogenic mutations are found in one of the mismatch repair genes. Downloaded from http://karger.com/ort/article-pdf/47/Suppl.

2 months ago

MSi-H Biomarker • Next-generation sequencing

MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)

MSI-H/dMMR • MSH2 mutation • MLH1 mutation

Ventana MMR RxDx Panel • TruSight Oncology 500 Assay • VENTANA anti-MSH2 (G219-1129) Mouse Monoclonal Primary Antibody • VENTANA anti-MSH6 (SP93) Rabbit Monoclonal Primary Antibody

2ms

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.

2 months ago

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

2ms

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

2 months ago

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

3ms

Rare germline mutation and MSH2-&MSH6 + expression in a double primary carcinoma of colorectal carcinoma and endometrial carcinoma: a case report. (PubMed, Diagn Pathol)

In the case of a patient with double primary EC and CRC, a careful evaluation of the IHC and the genetic data was presented. The patient carried rare compound heterozygous variants, a germline missense mutation, and a somatic frameshift mutation of MSH6, combined with a novel somatic null variant of MSH2. Our study broadened the variant spectrum of double primary cancer and provided insight into the molecular basis for abnormal MSH2 protein loss and double primary carcinoma.

3 months ago

Journal

MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • EPCAM (Epithelial cell adhesion molecule)

MSI-H/dMMR • MSH6 mutation • MSH2 mutation

3ms

Benign Adenomyoepithelioma: An Unrecognised Precursor of Ductal Carcinoma in Situ in Patient With Lynch Syndrome. (PubMed, Int J Surg Pathol)

Concordant loss of MSH2 in both lesions in the context of a MSH2 pathogenic variant in this patient with Lynch syndrome illustrates that the benign adenomyoepithelioma behaved as a likely precursor of DCIS. Our report provides a novel perspective that in some patients with Lynch syndrome adenomyoepithelioma may represent a pre-malignant precursor lesion of DCIS.

3 months ago

Journal

MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)

MSH2 mutation

3ms

High-throughput sequencing and in-silico analysis confirm pathogenicity of novel MSH3 variants in African American colorectal cancer. (PubMed, Neoplasia)

Overall, our data suggest that these variants among AA CRC patients affect the function of MSH3 making them pathogenic and likely contributing to the development or advancement of CRC among AA. Further clarifying functional studies will be necessary to fully understand the impact of these variants on MSH3 function and CRC development in AA patients.

3 months ago

Journal

MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH2 (MutS Homolog 2) • MSH3 (MutS Homolog 3)

MSH2 mutation

4ms

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

4 months ago

Trial completion • Trial completion date • Trial primary completion date

MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • EPCAM (Epithelial cell adhesion molecule)

MSI-H/dMMR • MSH2 mutation • MLH1 mutation • PMS2 mutation

4ms

Correlations between MSH2 and MSH6 Concentrations in Different Biological Fluids and Clinicopathological Features in Colorectal Adenocarcinoma Patients and Their Contribution to Fast and Early Diagnosis of Colorectal Adenocarcinoma. (PubMed, Biomedicines)

MSH6, which stands for mutS homolog 6, is not only useful in immunohistochemistry but in pathology practice as well. In this paper, the relationships between MSH6 levels in four biological fluids-whole blood, saliva, urine, and tissues-and tumor locations among the colorectal area, gross features, presence of a mucinous compound, molecular subtype, stroma features, and vascular invasions are presented.

4 months ago

Journal

MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CHEK2 (Checkpoint kinase 2)

MSH2 mutation

4ms

Susceptibility Genes Associated with Multiple Primary Cancers. (PubMed, Cancers (Basel))

This review aims to discuss these susceptibility genes and provide an explanation of their functions based on the signaling pathway background. Additionally, the association network between genetic signatures and different tumor pairs will be summarized.

4 months ago

Review • Journal • BRCA Biomarker

EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • MLH1 (MutL homolog 1) • MSH2 (MutS Homolog 2) • CHEK2 (Checkpoint kinase 2)

TP53 mutation • BRCA2 mutation • BRCA1 mutation • EGFR mutation • PTEN mutation • CHEK2 mutation • MSH2 mutation • MLH1 mutation

4ms

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

4 months ago

Trial completion date • Trial primary completion date

MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • EPCAM (Epithelial cell adhesion molecule)

MSI-H/dMMR • MSH2 mutation • MLH1 mutation • PMS2 mutation

4ms

Construction of a risk stratification model integrating ctDNA to predict response and survival in neoadjuvant-treated breast cancer. (PubMed, BMC Med)

In this study, we established a chemotherapy predictive model with a non-invasive tool that is built based on genomic features, ctDNA status, as well as clinical characteristics for predicting pCR to recognize the responders and non-responders to NAC, and also predicting prognosis for DFS in breast cancer. Adding pretreatment ctDNA levels to a model containing gene profile mutation and clinical characteristics significantly improves stratification over the clinical variables alone.

4 months ago

Journal • Circulating tumor DNA

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MSH2 (MutS Homolog 2) • IL7R (Interleukin 7 Receptor) • SETBP1 (SET Binding Protein 1) • NFKB1 (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1) • NOTCH4 (Notch 4) • FOXP1 (Forkhead Box P1)

TP53 mutation • EGFR mutation • PIK3CA mutation • MSH2 mutation

4ms

Defining molecular features associated with microsatellite instability and response to immune checkpoint blockade in urothelial carcinoma. (ASCO-GU 2024)

Targeted sequencing reveals distinct genomic features of MSI-H UC. The findings from this relatively large clinical cohort of MSI-H UC patients affirm previous associations between MSI status, TMB, and response to ICB in metastatic UC.

4 months ago

Checkpoint inhibition • Tumor mutational burden • Microsatellite instability • MSi-H Biomarker • Checkpoint block

TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • MSH2 (MutS Homolog 2)

MSI-H/dMMR • MSH2 mutation

5ms

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.

5 months ago

Clinical • MSi-H Biomarker

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)

MSI-H/dMMR • POLE mutation • MSH6 mutation • MSH2 mutation • MLH1 mutation • POLD1 mutation • PMS2 mutation • POLE mutation + POLD1 mutation

5ms

Liquid biopsy-based comprehensive genomic profiling to reveal mutational landscape in real-world patients with gastrointestinal cancer. (ASCO-GI 2024)

This study elucidated the comprehensive mutational landscape of advanced gastrointestinal cancer through liquid biopsy, thereby contributing novel biomarkers for clinical diagnosis and facilitating targeted therapy mechanism investigations.

5 months ago

Real-world evidence • Clinical • Tumor mutational burden • BRCA Biomarker • Liquid biopsy • Real-world • Biopsy

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • ARID1A (AT-rich interaction domain 1A) • MLH1 (MutL homolog 1) • FGFR4 (Fibroblast growth factor receptor 4) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • FAT1 (FAT atypical cadherin 1) • EPCAM (Epithelial cell adhesion molecule) • ERCC5 (ERCC Excision Repair 5 Endonuclease 2)

EGFR mutation • HRD • MSH6 mutation • MSH2 mutation • MLH1 mutation • PMS2 mutation

PredicineCARE™

5ms

A locally advanced colon cancer patient with Muir-Torre syndrome obtains durable response to neoadjuvant and adjuvant immunotherapy. (PubMed, Tumori)

The results demonstrate promising performance in neoadjuvant and adjuvant settings. Further studies are needed to confirm its potential usefulness as an outcome measure in clinical practice.

5 months ago

Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker • Metastases

TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • MSH2 (MutS Homolog 2)

TMB-H • MSI-H/dMMR • MSH2 mutation

Keytruda (pembrolizumab)

5ms

A Comprehensive Study of Heterogeneous Mismatch Repair Expression in Solid Tumors Reveals Different Immunohistochemical Patterns and Distinct Genetic Mechanisms. (PubMed, Am J Surg Pathol)

Our findings highlighted the importance of accurately interpreting heterogeneous MMR protein staining patterns for developing a more efficient personalized genetic investigation strategy.

5 months ago

Journal • Mismatch repair • Tumor mutational burden

TMB (Tumor Mutational Burden) • 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 • MLH1 mutation • PMS2 mutation • POLE EDM

5ms

Pilot Study of Nivolumab in Pediatric Patients With Hypermutant Cancers (clinicaltrials.gov)

P1/2, N=11, Terminated, The Hospital for Sick Children | N=50 --> 11 | Trial completion date: Sep 2022 --> Nov 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Sep 2022 --> Nov 2023; Withdrawal of drug supply/funding

5 months ago

Enrollment change • Trial completion date • Trial termination • Trial primary completion date • IO biomarker

TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • POLD1 (DNA Polymerase Delta 1) • EPCAM (Epithelial cell adhesion molecule) • MSH3 (MutS Homolog 3) • APOB (Apolipoprotein B)

MSI-H/dMMR • POLE mutation • MSH2 mutation • POLD1 mutation • PMS2 mutation • EPCAM expression

Opdivo (nivolumab)

5ms

Genomic characterization of IDH-mutant astrocytoma progression to grade 4 in the treatment setting. (PubMed, Acta Neuropathol Commun)

All patients in our discovery cohort received radiation, all but one underwent chemotherapy, and no patient received temozolomide (TMZ) before progression to grade 4 disease...In our retrospective analysis of patient treatment and survival timelines (n = 75), the combination of postoperative radiation and chemotherapy (mainly TMZ) outperformed radiation, especially in the grade 3 tumor cohort, in which it was typically given after primary surgery. Our results provide further insight into the contribution of treatment and genetic alterations in cell cycle, growth factor signaling, and DNA repair-related genes to tumor evolution and progression.

5 months ago

Journal

MET (MET proto-oncogene, receptor tyrosine kinase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • DNMT3A (DNA methyltransferase 1) • RB1 (RB Transcriptional Corepressor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • MSH2 (MutS Homolog 2) • RAD51B (RAD51 Paralog B) • NRG3 (Neuregulin 3)

CDKN2A deletion • MSH2 mutation • NRG3 deletion

temozolomide

6ms

Prognostic impact of tumor mutational burden at baseline in IDH-wildtype glioblastoma (SNO 2023)

In summary, there is no significant association between TMB at baseline and poor survival outcomes in IDH-wildtype GBM. Further research is needed to explore the potential implications of TMB as a prognostic marker and its relevance for personalized treatment strategies in GBM patients.

6 months ago

Tumor mutational burden

TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)

MSH2 mutation • MLH1 mutation • PMS2 mutation • IDH wild-type

OncoPanel™ Assay

6ms

DEFINING THE IMPACT OF PERSONAL AND FAMILY HISTORY OF LYNCH-SYNDROME ASSOCIATED CANCERS ON CLINICAL CHARACTERISTICS AND OUTCOMES OF PATIENTS WITH UPPER TRACT UROTHELIAL CARCINOMA (SUO 2023)

Factors that may be associated with lower complete and partial response in the NAC and higher risk of metastatic recurrence in the AC cohorts included history of Lynch, smoking history, and preoperative hydronephrosis whereas cisplatin-based chemotherapy may be associated with better outcomes (Table 2)... LS-related UTUC may have distinct biologic behavior and responses to chemotherapy than sporadic UTUC. Given the superior outcomes seen with immunotherapy in metastatic disease and the approved indication for this treatment in those with LS, proper identification of LS-related UTUC is imperative in order to evaluate this paradigm further in the non-metastatic setting. This can be most reliably achieved with universal tumor testing and confirmatory germline sequencing.

6 months ago

Clinical • IO biomarker

MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)

MSH2 mutation • MLH1 mutation • PMS2 mutation

cisplatin

6ms

Unique molecular signatures of germline mutations in low expression of human epidermal growth factor receptor 2 (HER2) breast cancer (SABCS 2023)

HER2-low BC patients have distinct germline mutational signatures and differential clinical outcomes under neoadjuvant systemic therapy. These results have provided additional evidence that HER2-low patients comprise a fourth subtype of BC that needs to be accounted for separately in terms of clinical treatment and outcome reporting.

6 months ago

BRCA Biomarker

HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • MSH2 (MutS Homolog 2) • ERCC1 (Excision repair cross-complementation group 1) • PMS2 (PMS1 protein homolog 2) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51C (RAD51 paralog C) • MRE11A (MRE11 homolog, double strand break repair nuclease) • MUTYH (MutY homolog) • FANCI (FA Complementation Group I) • FANCM (FA Complementation Group M) • FLCN (Folliculin) • FANCD2 (FA Complementation Group D2) • RECQL4( RecQ Like Helicase 4) • BMPR1A (Bone Morphogenetic Protein Receptor Type 1A) • RAD54B (RAD54 Homolog B)

BRCA1 mutation • EGFR mutation • HER-2 overexpression • HER-2 mutation • HER-2 expression • ATM mutation • PALB2 mutation • MSH2 mutation • RAD51C mutation • FANCA mutation • PMS2 mutation • FANCI mutation • FANCM mutation • RAD51 mutation • RECQL4 mutation

6ms

Evaluation of Three Methods for Lynch Syndrome Screening in Patients with Colorectal Cancer (AMP 2023)

The Promega OncoMate MSI Dx analysis system shows excellent concordance with the previous Promega MSI analysis system v1.2 and MMR IHC in CRC tumor samples, and has clinical utility in screening for LS in CRC patients.

6 months ago

Clinical • MSi-H Biomarker

MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)

MSI-H/dMMR • MSH2 mutation • MLH1 mutation • PMS2 mutation

OncoMate™ MSI

6ms

Lynch syndrome-associated upper tract urothelial carcinoma frequently occurs in patients older than 60 years: an opportunity to revisit urology clinical guidelines. (PubMed, Virchows Arch)

Using current screening guidelines, a significant proportion of patients with LS-associated UTUC may be missed. We suggest universal immunohistochemical MMRp screening for all UTUCs, regardless of age and clinical history.

6 months ago

Clinical guideline • Journal

MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)

MSH6 mutation • MSH2 mutation

6ms

CLINICAL FEATURES OF CANCERS DIAGNOSED IN PATIENTS WITH LYNCH SYNDROME-ASSOCIATED GENE GERMLINE MUTATIONS (IGCS 2023)

Among a total of 112 patients diagnosed with Lynch syndrome, 36 (32.14%) patients were MLH1 variants, 38 (33.92%) patients had mutation in the MSH2 gene. And 16 (14.28%) patients had mutation in the MSH6 gene, 15 (13.39%) patients were PMS2. Pathogenic MLH1 and MSH2 variants caused high penetrance dominant cancer syndromes sharing similar colorectal, endometrial cancer risks, but pathogenic MSH6, PMS2 variants caused high penetrance endometrial, ovary cancers.

6 months ago

Clinical

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

6ms

Microsatellite instability and mismatch repair deficiency define a distinct subset of lung cancers characterized by smoking exposure, high tumor mutational burden and recurrent somatic MLH1 inactivation. (PubMed, J Thorac Oncol)

We present a comprehensive clinico-genomic landscape of MSI-H/MMR-D lung cancers and demonstrate that MSI-H/MMR-D defines a rare subset of lung cancers associated with smoking, high TMB, and MLH1 inactivation. While DCB to ICI was observed in some patients, the broad range of responses suggests that clinical activity may be modulated by co-mutational landscapes.

6 months ago

Journal • Mismatch repair • Tumor mutational burden • Microsatellite instability • MSi-H Biomarker

TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1) • MLH1 (MutL homolog 1) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • JAK1 (Janus Kinase 1)

TMB-H • MSI-H/dMMR • STK11 mutation • KEAP1 mutation • MSH2 mutation • PMS2 mutation • JAK1 mutation

6ms

The prevalence of lynch syndrome (DNA mismatch repair protein deficiency) in patients with primary localized prostate cancer using immunohistochemistry screening. (PubMed, Hered Cancer Clin Pract)

In this study, immunohistochemical screening of MMR proteins for Lynch syndrome was performed in a series of prostate cancer cases. The prevalence of Lynch syndrome in localized prostate cancer was 0.8%, which is low compared with other Lynch syndrome-associated cancers.

6 months ago

Journal • Mismatch repair

MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)

MSH2 mutation • MSH6 expression

7ms

Constitutional Mismatch Repair Deficiency Syndrome as a Cause of Numerous Malignancies in a Teenage Patient-A Case Report. (PubMed, J Pediatr Hematol Oncol)

Due to the almost exceeded total dose of anthracyclines, the patient's treatment included blinatumomab, and subsequently, he was qualified for allogeneic hematopoietic cell transplantation. The patient remains in complete remission for 11 months after allogeneic hematopoietic stem cell transplantation under the care of the transplant center.

7 months ago

Journal • Mismatch repair

MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)

MSH2 mutation • MLH1 mutation • PMS2 mutation

Blincyto (blinatumomab)

7ms

Genetic analysis of fundic gland‑type gastric adenocarcinoma. (PubMed, Mol Clin Oncol)

GAFG exhibits diversity at the molecular level, and GNAS mutations are more common than KRAS mutations, TP53 mutations, and microsatellite instability. To date, no association between EBV/HER2 and GAFG has been found.

7 months ago

Journal

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • PMS2 (PMS1 protein homolog 2) • GNAS (GNAS Complex Locus)

TP53 mutation • KRAS mutation • BRAF mutation • NRAS mutation • PIK3CA mutation • APC mutation • CTNNB1 mutation • MSH2 mutation • PMS2 mutation • GNAS mutation

7ms

The Link Between Sebaceous Adenomas in Unusual Locations and Colorectal Tumors: A Case Study of Muir-Torre Syndrome (ASDP 2023)

MTS is a unique condition that necessitates continuous surveillance. When sebaceous adenoma arises in atypical regions, it is important to consider additional screening to eliminate the likelihood of MTS. Poster type: Poster Defense

7 months ago

Clinical

MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)

MSH2 mutation • MSH6 expression