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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:
Related biomarkers:
18h
New trial • IO biomarker
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EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • RUNX3 (RUNX Family Transcription Factor 3) • IL1B (Interleukin 1, beta) • NLRP3 (NLR Family Pyrin Domain Containing 3) • NEUROG1 (Neurogenin 1)
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PD-L1 expression • TP53 mutation • KRAS mutation • EGFR mutation • MSI-H/dMMR • BRAF mutation • EGFR expression • PMS2 mutation • TP53 expression • PD-L1 mutation
9d
A Phase IIa Randomized, Double-Blinded Clinical Trial of Naproxen or Aspirin for Cancer Immune Interception in Lynch Syndrome (clinicaltrials.gov)
P2a, N=40, Not yet recruiting, M.D. Anderson Cancer Center | Initiation date: Nov 2022 --> Nov 2023
Trial initiation date
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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 • MSH2 mutation • MLH1 mutation • PMS2 mutation
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aspirin • naproxen
16d
Cancer Preventive Vaccine Nous-209 for Lynch Syndrome Patients (clinicaltrials.gov)
P1/2, N=45, Recruiting, National Cancer Institute (NCI) | Phase classification: P2 --> P1/2
Phase classification • IO biomarker
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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
19d
A dedicated screening for early detection of Prostate cancer (Pca) in men with germline mutations in DNA-Repair Genes (DRG) (EMUC 2022)
An accurate evaluation of the genealogical trees of breast/ovarian cancer BRCA1-2 mutated patients and relatives of men with PCa and DRG mutation allows the detection of men potentially carriers of DRG mutations and consequently enroll them in a dedicated screening, currently absent. As a result, we set out to design a screening based on PHI and MRI aiming to improve the capacity of early diagnosis as well as creating a potentially personalized approach.
BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MLH1 (MutL homolog 1) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1)
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BRCA2 mutation • BRCA1 mutation • BRIP1 mutation • MSH2 mutation • MLH1 mutation • PMS2 mutation
19d
DNA mismatch repair testing in upper tract urothelial carcinoma patients - Is Universal Lynch Syndrome screening necessary? (EMUC 2022)
Since screening with the Amsterdam II criteria seems to be unhelpful with no significant difference in age of onset, we propose to routinely screen all new UTUC cases on MMR deficiency using immunohistochemical methods similar to those in place for colorectal and endometrial carcinoma. The fact that in most cases MMR deficiency in UTUC is based on a germline mutation, underlines the importance of universal LS screening in UTUC patients.
Clinical • Mismatch repair
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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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MSH2 mutation • PMS2 mutation
19d
Concurrent loss of MLH1, PMS2 and MSH6 immunoexpression in digestive system cancers indicating a widespread dysregulation in DNA repair processes. (PubMed, Front Oncol)
The affected MMR/HRR-related genes were: ATM, BARD1, BRCA1, CDK12, CHEK1, CHEK2, FANCA, MLH1, MSH6, PALB2, TP53. Considering the biologic function of HRR/MMR proteins as potential drug targets and the low frequency of most of these mutations in digestive system cancers in general, their common occurrence in our MLH1/PMS2/MSH6 cases seems to be even more noteworthy, highlighting the need for recognition, awareness and further investigation of this unusual IHC staining pattern.
Journal • BRCA Biomarker
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BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • MSI (Microsatellite instability) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1)
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MSI-H/dMMR • FANCA mutation • PMS2 mutation • BRAF exon 15 mutation
1m
The Role of Adult Cancer Predisposition Genes in Hematological Malignancies of Childhood (ASH 2022)
Interestingly, 4/5 patients with a pathogenic variant had a BCP-ALL and 1/5 had a BCR-ABL CML that rapidly progressed to lymphoid blast crisis while under imatinib therapy (400 mg/m2)... We diagnosed a classical cancer predisposition syndrome associated with the respective hematological malignancy in 5/162 patients (3%): Li-Fraumeni (N=1), Constitutional mismatch repair deficiency (CMMRD) (N=1), Nijmegen-Breakage syndrome (NBS) (N=1) and Noonan syndrome (N=2). Additionally we identified in 19/162 patients a pathogenic / likely pathogenic variant (P/LP) in one of the ACGs, including BRIP1, CHEK2, HOXB13, BRCA1, MSH2 and STK11. Strikingly, we observed a high frequency of CHEK2 germline variants in our cohort (15/162) (Figure 1A).
Clinical • BRCA Biomarker
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • STK11 (Serine/threonine kinase 11) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • GAPDH (Glyceraldehyde-3-Phosphate Dehydrogenase) • HOXB13 (Homeobox B13)
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MSH2 mutation • MLH1 mutation • PMS2 mutation
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imatinib
1m
Teenage-Onset Colorectal Cancers in a Digenic Cancer Predisposition Syndrome Provide Clues for the Interaction between Mismatch Repair and Polymerase δ Proofreading Deficiency in Tumorigenesis. (PubMed, Biomolecules)
Taken together, these patients represent the first cases of cancer predisposition due to heterozygous variants in PMS2 and POLD1. Analysis of their CRCs supports that POLD1-mutated tumors acquire hypermutation only with concurrent MMRd.
Journal • Mismatch repair
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MLH1 (MutL homolog 1) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • POLD1 (DNA Polymerase Delta 1)
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PMS2 mutation
1m
GENERATE: GENetic Education Risk Assessment and TEsting Study (clinicaltrials.gov)
P=N/A, N=1000, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Jun 2023 --> Dec 2027
Trial completion date
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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)
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TP53 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • APC mutation • MSH2 mutation • PMS2 mutation
1m
Performance of MSI Testing by the Automated Rapid Idylla Assay in Comparison with the Promega Assay in MMR-Deficient Endometrial Carcinomas (AMP 2022)
The findings highlight challenges in MSI detection in endometrial cancer using PCR-based methods. The imperfect correlation between IHC for MMR and molecular MSI testing has been acknowledged. The automated rapid Idylla MSI assay yields negative results in more than 60% of dMMR endometrial cancer cases when manufacturer's instructions are followed.
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 • MSH6 mutation • MLH1 mutation • PMS2 mutation
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Idylla™ MSI Test
2ms
Efficacy of platinum-based chemotherapy and germline mutational status in early-stage triple-negative breast cancer: a unicenter retrospective analysis with long-term follow-up (SABCS 2022)
BACKGROUND: In early-stage triple negative breast cancer (TNBC), the addition of carboplatin(CBDCA) to neoadjuvant chemotherapy (CT) increases pathologic complete response (pCR)and relapsed-free survival... The addition of CBDCA to standard CT was significantly associated with pCRand RFS but not OS, consistent with the phase III data. The benefit in terms of RFS wasindependent of the presence and the type of pathogenic germline alterations.
Retrospective data • BRCA Biomarker
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TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • 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)
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TP53 mutation • PALB2 mutation • PMS2 mutation
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carboplatin
2ms
BAT26 Only Microsatellite Instability with High Tumor Mutation Burden-A Rare Entity Associated with PTEN Protein Loss and High PD-L1 Expression. (PubMed, Int J Mol Sci)
In conclusion, BAT26-only instability is very rare and associated with PTEN protein loss, high TMB, and a high PD-L1 score. Our results suggest that patients with BAT26-only instability may show good responses to immunotherapy.
Journal • Tumor Mutational Burden • Microsatellite instability • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • MLH1 (MutL homolog 1) • PMS2 (PMS1 protein homolog 2)
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PD-L1 expression • KRAS mutation • TMB-H • PD-L1 overexpression • PTEN mutation • PMS2 mutation • KRAS A146T
2ms
Cancer Preventive Vaccine Nous-209 for Lynch Syndrome Patients (clinicaltrials.gov)
P2, N=45, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting | Trial completion date: Dec 2024 --> Jul 2025 | Initiation date: Feb 2023 --> Sep 2022 | Trial primary completion date: Dec 2024 --> Jul 2025
Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • IO biomarker
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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
2ms
Exome sequencing in a Swedish family with PMS2 mutation with varying penetrance of colorectal cancer: investigating the presence of genetic risk modifiers in colorectal cancer risk. (PubMed, Eur J Cancer Prev)
We conclude the genetic architecture behind the incomplete penetrance of PMS2 is complicated and must be assessed in a genome wide manner using large families and multifactorial analysis.
Journal
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PMS2 (PMS1 protein homolog 2) • NFKB1 (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1) • BAG1 (BAG Cochaperone 1)
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PMS2 mutation
3ms
Fertility-sparing treatment for endometrial cancer and atypical endometrial hyperplasia in patients with Lynch Syndrome: Molecular diagnosis after immunohistochemistry of MMR proteins. (PubMed, Front Med (Lausanne))
None of the patients achieved pregnancy, and those who responded to treatment had subsequent relapse of disease. Patients undergoing fertility-sparing treatment for atypical endometrial hyperplasia and endometrial cancer should perform MMR immunohistochemical analysis in order to screen LS.
Journal
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MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
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MSH2 mutation • PMS2 mutation
3ms
Bi allelic loss of MSH2 in endometrial carcinoma, a case report (ESGO 2022)
MMR gene alterations (hMLH1/hMSH2) play an important role in the development of MSI in sporadic EAC. Most presumed sporadic, MSI-positive EACs are associated with epigenetic silencing of MLH1, via promoter hypermethylation. A smaller fraction have somatic mutations in MSH6, or loss of MSH2 protein expression.
Clinical
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ER (Estrogen receptor) • MSI (Microsatellite instability) • 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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ER positive • TP53 wild-type • MSH6 mutation • MSH2 mutation • MLH1 mutation • PMS2 mutation
3ms
Trial initiation date
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MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • EPCAM (Epithelial cell adhesion molecule)
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MSH2 mutation • MLH1 mutation • PMS2 mutation
3ms
Testing the Combination of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) in Children, Adolescent, and Young Adult Patients With Relapsed/Refractory Cancers That Have an Increased Number of Genetic Changes, The 3CI Study (clinicaltrials.gov)
P1, N=0, Withdrawn, National Cancer Institute (NCI) | N=26 --> 0 | Trial completion date: Jun 2024 --> Jun 2022 | Active, not recruiting --> Withdrawn | Trial primary completion date: Jun 2024 --> Jun 2022
Enrollment change • Trial completion date • Trial withdrawal • Trial primary completion date • IO biomarker
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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) • MSH3 (MutS Homolog 3)
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MSI-H/dMMR • POLD1 mutation • MSH2 mutation • PMS2 mutation • EPCAM expression • MSH6 expression
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Opdivo (nivolumab) • Yervoy (ipilimumab)
3ms
Gastric Cancer Risk Estimates in Hereditary Cancer Syndromes: A Systematic Review (ACG 2022)
The literature search revealed 2,494 observational studies, of which 26 met inclusion criteria for full-text abstraction. For HDGC, ranges for cumulative incidence of diffuse gastric cancer (DGC) varied widely across four studies. In men, four studies showed cumulative incidence by the eighth decade of life ranged from 37.2% (95% CI, 8.7-89.5) to 70.0% (95% CI, 40-94), while ranges for women were uniformly lower by the eighth decade, ranging from 24.7% (95% CI 6.1-68.9) to 63% (95% CI 19-99).
Review • BRCA Biomarker
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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) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • SMAD4 (SMAD family member 4) • MSH2 (MutS Homolog 2) • CDH1 (Cadherin 1) • PMS2 (PMS1 protein homolog 2) • APC (APC Regulator Of WNT Signaling Pathway) • BRCA (Breast cancer early onset) • MUTYH (MutY homolog) • CTNNA1 (Catenin Alpha 1) • PRSS1 (Serine Protease 1)
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TP53 mutation • BRCA2 mutation • BRCA1 mutation • PALB2 mutation • APC mutation • MSH6 mutation • MSH2 mutation • MLH1 mutation • PMS2 mutation • BRCA mutation • CDH1 mutation
4ms
Microsatellite instability in intestinal T-cell lymphomas (ECP 2022)
Taken together, these data reveal a relatively high TMB in ITCLs when compared to other peripheral T-cell lym-phomas, and an MSI status in a subset of MEITLs. This suggests a role of MMR deficiency in the oncogenesis of a proportion of ITCLs, with potential clinical implications. Alternative muta-genic mechanisms, possibly involving the intestinal environ-ment, seem to play a role in the tumorigenesis of the majority of ITCLs.
Tumor Mutational Burden • Microsatellite instability
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TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
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TMB-H • MSH2 mutation • MLH1 mutation • PMS2 mutation
4ms
Concurrent loss of MLH1, PMS2 and MSH6 immunoexpression in gastrointestinal cancer indicating a widespread dysregulation in DNA reparation processes (ECP 2022)
Our study suggests that the simultaneous loss of MLH1, PMS2 and MSH6 immunoexpression among diferent gastrointesti-nal cancers is associated with and potentially even based on more widespread alterations in DNA repair processes. Next-generation sequencing could reveal further mutations in additional DNA repair-related genes in the present cases. With the advent of drugs targeting DNA repair in clinical practice, especially PARP-inhibitors, and their potential indication extension for mutations other than BRCA1/2 such as PALB2 our results are of immediate clinical signifcance.
BRCA Biomarker • PARP Biomarker
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BRAF (B-raf proto-oncogene) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • FANCA (FA Complementation Group A) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1)
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BRAF V600E • BRCA2 mutation • BRCA1 mutation • BRAF V600 • ATM mutation • PALB2 mutation • FANCA mutation • RAD51D mutation • PMS2 mutation • BARD1 mutation • RAD54L mutation • CHEK1 mutation • CHEK1 expression • MSH6 expression
4ms
Medullary carcinoma of the pancreas: a case report and review of the literature (ECP 2022)
Medullary carcinoma of the pancreas is a rare entity associated with microsatellite instability, mismatch repair defects, colorectal adenocarcinoma and familial syndromes. Our case demonstrates classical morphological features including dense tumour infiltrating lymphocytes, poorly differentiated epithelial cells with syncytial growth and pushing borders. Following diagnosis, genetic counselling should be considered to exclude Lynch syndrome as this may be the first sign of an inherited cancer syndrome.
Clinical • Review
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BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • PMS2 (PMS1 protein homolog 2) • CDX-2 • MUC4 (Mucin 4, Cell Surface Associated) • MUC2 • CA 19-9 (Cancer antigen 19-9)
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BRAF mutation • NRAS mutation • PMS2 mutation • MUC2 negative
4ms
Cancer Preventive Vaccine Nous-209 for Lynch Syndrome Patients (clinicaltrials.gov)
P2, N=45, Not yet recruiting, National Cancer Institute (NCI) | Initiation date: Sep 2022 --> Feb 2023
Trial initiation date • IO biomarker
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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
4ms
Identification of Lynch Syndrome in Patients with Endometrial Cancer Based on a Germline Next Generation Sequencing Multigene Panel Test. (PubMed, Cancers (Basel))
Non-endometrioid histology was more prevalent in patients with MSH6 or PMS2 mutations (41.7%) than those with MLH1 or MSH2 mutations (5.6%, p = 0.026). In this pre-selected cohort of endometrial cancer patients who underwent next generation sequencing, the prevalence of LS was 13%, thus supporting the use of gene panel testing for endometrial cancer patients.
Journal • Next-generation sequencing
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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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MSH6 mutation • MSH2 mutation • MLH1 mutation • PMS2 mutation
4ms
Analysis of PMS2 mutation as a potential biomarker for melanoma immunotherapy (ESMO 2022)
Analysis of discovery and validation cohort data shows PMS2 mutation is associated with better OS in ICI-treated patients. These findings indicates that PMS2 mutation may serve as a potential predictive biomarker for ICIs in melanoma.
Tumor Mutational Burden • IO biomarker
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TMB (Tumor Mutational Burden) • PMS2 (PMS1 protein homolog 2)
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TMB-H • PMS2 mutation
5ms
Genotypes of Papillary Thyroid Carcinoma With High Lateral Neck Metastasis in Chinese Population. (PubMed, Front Oncol)
When combined with the TERT mutations, the BRAF mutation group was prone to lateral lymph node metastasis, particularly in elderly women. The NF1 mutations usually co-existed with PMS2 mutations, and this group included more men and young patients who had a high tumor mutational burden and lateral lymph node metastasis rate.
Journal • Tumor Mutational Burden
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BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • NF1 (Neurofibromin 1) • TERT (Telomerase Reverse Transcriptase) • PMS2 (PMS1 protein homolog 2)
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BRAF V600E • TMB-H • BRAF V600 • NF1 mutation • PMS2 mutation • TERT mutation
5ms
New trial
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • STK11 (Serine/threonine kinase 11) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • EPCAM (Epithelial cell adhesion molecule)
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BRCA1 mutation • STK11 mutation • PALB2 mutation • MSH2 mutation • PMS2 mutation
5ms
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: Apr 2022 --> Apr 2023 | Trial primary completion date: Apr 2022 --> Apr 2023
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
5ms
Pediatric T-ALL type-1 and type-2 relapses develop along distinct pathways of clonal evolution. (PubMed, Leukemia)
Deconvolution analysis of ATAC-Seq profiles showed that T-ALLs later developing into type-1 relapses resembled a predominant immature thymic T-cell population, whereas T-ALLs developing into type-2 relapses resembled a mixture of normal T-cell precursors. In sum, our analyses revealed fundamentally different mechanisms driving either type-1 or type-2 T-ALL relapse and indicate that differential capacities of disease evolution are already inherent to the molecular setup of the initial leukemia.
Journal
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TP53 (Tumor protein P53) • ABCB1 (ATP Binding Cassette Subfamily B Member 1) • PMS2 (PMS1 protein homolog 2) • NT5C2 (5'-Nucleotidase Cytosolic II) • IL7R (Interleukin 7 Receptor) • MVP (Major Vault Protein) • BUB1B (BUB1 Mitotic Checkpoint Serine/Threonine Kinase B)
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TP53 mutation • PMS2 mutation • BLM mutation
5ms
Enrollment closed • IO biomarker
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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) • MSH3 (MutS Homolog 3)
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MSI-H/dMMR • POLD1 mutation • MSH2 mutation • PMS2 mutation • EPCAM expression • MSH6 expression
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Opdivo (nivolumab) • Yervoy (ipilimumab)
5ms
A common genetic variant of the gene encoding Granzyme B associates with cancer risk in patients with Lynch syndrome (EACR 2022)
Granzyme B might be involved in the modification of several MSI-H associated neoantigens. Funding The authors would like to acknowledge the financial support of the Ministry of Innovation and Technology (NLP-17; NKFIH-FK-21-138377; ÚNKP-21-5-SE-21) and of the Hungarian Academy of Sciences (BO/00141/21).
Clinical • Tumor Mutational Burden • MSi-H Biomarker • IO biomarker
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TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • GZMB (Granzyme B)
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TMB-H • MSI-H/dMMR • MSH2 mutation • MLH1 mutation • PMS2 mutation
6ms
Comprehensive Genomic Profiling of Tumor Mutational Burden-high in Chinese Lung Cancer Patients (IASLC-WCLC 2022)
TMB-H is relatively higher in Chinese lung cancer male patients, and it can be seen in various pathological subtypes. TMB-H may coexist with both gene mutations positively associated with immunotherapy and driver alterations negatively associated with immunotherapy. Our results revealed the potential immunotherapy strategies among TMB-H population with lung cancer should be considered in further study.
Clinical • Tumor Mutational Burden • IO biomarker
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • RB1 (RB Transcriptional Corepressor 1) • POLE (DNA Polymerase Epsilon) • KMT2D (Lysine Methyltransferase 2D) • LRP1B (LDL Receptor Related Protein 1B) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • KMT2C (Lysine Methyltransferase 2C) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • MLL2 (Myeloid/lymphoid or mixed-lineage leukemia 2) • SOX2 • AGO2 (Argonaute RISC Catalytic Component 2)
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TP53 mutation • TMB-H • BRAF mutation • HER-2 amplification • PIK3CA mutation • BRAF V600 • EGFR exon 19 deletion • RET fusion • ALK fusion • ROS1 fusion • KMT2D mutation • PMS2 mutation • ALK-ROS1 fusion
6ms
Stand up to Cancer: MAGENTA (Making Genetic Testing Accessible) (clinicaltrials.gov)
P1, N=4000, Recruiting, M.D. Anderson Cancer Center | Unknown status --> Recruiting | Trial completion date: Apr 2022 --> Apr 2023 | Trial primary completion date: Apr 2021 --> Apr 2023
Enrollment open • Trial completion date • Trial primary completion date
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ER (Estrogen receptor) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1)
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BRCA2 mutation • BRCA1 mutation • PALB2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • MSH2 mutation • MLH1 mutation • PMS2 mutation • BARD1 mutation • RAD51 mutation
6ms
DAXX, ATRX, and MSI in PanNET and Their Metastases: Correlation with Histopathological Data and Prognosis. (PubMed, Pathobiology)
Our study supports the hypothesis that a loss of DAXX immunoreactivity can identify a more aggressive subtype of PanNET with high confidence, while ATRX loss is a weaker indicator. Our results also strengthen the role of DAXX immunolabeling as a prognostic marker. We could show that ATRX might be less suitable as a surrogate for sequencing. Our results indicate that IHC of DAXX and ATRX may identify PanNET subtypes as targets for more aggressive therapy.
Journal
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MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • ATRX (ATRX Chromatin Remodeler) • PMS2 (PMS1 protein homolog 2) • DAXX (Death-domain associated protein)
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ATRX mutation • MSH2 mutation • MLH1 mutation • PMS2 mutation
6ms
New P2a trial
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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 • MSH2 mutation • MLH1 mutation • PMS2 mutation
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aspirin • naproxen
6ms
New trial
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MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • EPCAM (Epithelial cell adhesion molecule)
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MSH2 mutation • MLH1 mutation • PMS2 mutation
6ms
Biallelic mismatch repair deficiency - A rare and trouble genetic syndrome. (PubMed, Rev Esp Enferm Dig)
MMR immunohistochemical shows a hallmark pattern with absence of staining in both neoplastic and non-neoplastic cells for the biallelic mutated gene. We present a unique case of a young boy diagnosed with invasive colon adenocarcinoma and brain tumor, with classical BMMRD features, found to have biallelic pathogenic PMS2 mutations.
Journal • Mismatch repair
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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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MSH2 mutation • MLH1 mutation • PMS2 mutation
6ms
Utility of germline multi-gene panel testing in patients with endometrial cancer. (PubMed, Gynecol Oncol)
Germline MGPT is both feasible and informative as it identifies LS cases not found on tumor testing as well as additional actionable mutations in patients with EC.
Retrospective data • 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) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • EPCAM (Epithelial cell adhesion molecule)
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BRCA2 mutation • ATM mutation • CHEK2 mutation • RAD51C mutation • MSH2 mutation • MLH1 mutation • PMS2 mutation
7ms
Risk of first onset of colorectal cancer associated with alcohol consumption in Lynch syndrome: a multicenter cohort study. (PubMed, Int J Clin Oncol)
Alcohol consumption was associated with earlier onset of the first CRC in Japanese LS cohort. The association was stronger in men, carriers of pathogenic MLH1 and MSH2 mutations, and tumors located in the proximal colon. Our findings illuminate the mechanism of LS-associated carcinogenesis and serve as a recommendation for discontinuing or ceasing alcohol consumption.
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
7ms
Pilot Study of Nivolumab in Pediatric Patients With Hypermutant Cancers (clinicaltrials.gov)
P1/2, N=50, Active, not recruiting, The Hospital for Sick Children | Trial completion date: Sep 2021 --> Sep 2022 | Trial primary completion date: Sep 2021 --> Sep 2022
Trial completion date • Trial primary completion date • IO biomarker
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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) • MSH3 (MutS Homolog 3) • EPCAM (Epithelial cell adhesion molecule) • APOB (Apolipoprotein B)
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MSI-H/dMMR • POLE mutation • POLD1 mutation • MSH2 mutation • PMS2 mutation • EPCAM expression
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Opdivo (nivolumab)
7ms
Genomic landscape of microsatellite instability in Chinese tumors: a comparison of Chinese and TCGA cohorts. (PubMed, Int J Cancer)
Mutations in ACVR2A (73% vs 28%, p <0.01) and MMR-related genes (51.4% vs 21.3%, p <0.01) were significantly higher in the Chinese population. Thus, our study suggests the fraction of MSI-H attributable to MMR inactivation mutations were lower in European than in Chinese patients, while the proportion of MSI-H due to other events may be higher.
Journal • Tumor Mutational Burden • Microsatellite instability • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • KMT2D (Lysine Methyltransferase 2D) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • ACVR2A (Activin A Receptor Type 2A)
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PD-L1 expression • TMB-H • PD-L1 overexpression • MSI-H/dMMR • MSH2 mutation • PMS2 mutation