News - PMS1 mutation - LARVOL VERI

almost2years

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

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

almost 2 years 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-actl)

2years

Prevalence of genomic alterations in Xerna tumor microenvironment subtypes in triple negative breast cancer patients (SABCS 2023)

The Xerna TME Panel classified 49.3% of TNBC patient tumors to IA or IS, suggesting they may respond to ICI therapy. Many (56.2%) patient tumors harbored alterations associated with FDA-approved therapies, providing the potential for novel combination therapies. These findings warrant further study and clinical validation in TNBC patients treated with ICI therapy.

2 years ago

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

PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS1 (PMS1 protein homolog 1)

TMB-H • PMS1 mutation

OncoExTra™ test • Xerna TME™ Panel

over2years

A unique case of rectal cancer with coexistence of multiple pathways of carcinogenesis. (PubMed, World J Surg Oncol)

The case is unique suggesting a possible interaction between the two pathways and contributing to carcinogenesis in this patient. This also suggests need for a thorough germline and somatic mutation evaluation in select colorectal cancer patients to direct a tailored therapy.

over 2 years ago

Journal

TP53 (Tumor protein P53) • MSH6 (MutS homolog 6) • APC (APC Regulator Of WNT Signaling Pathway) • PMS1 (PMS1 protein homolog 1)

TP53 mutation • APC mutation • MSH6 mutation • PMS1 mutation

capecitabine

over2years

ANALYSIS OF THE MOLECULAR PROFILE OF ENDOMETRIAL CANCER DEPENDING ON MICROSATELITE INSTABILITY (ESGO 2023)

A higher frequency of deletions with the displacement of the reading frame is observed in the SI cohort. TMB index in IM reveals tumors with MI have a better response to treatment with immune checkpoint inhibitors.

over 2 years ago

Tumor mutational burden • IO biomarker

TP53 (Tumor protein P53) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • MLH1 (MutL homolog 1) • KMT2D (Lysine Methyltransferase 2D) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • JAK1 (Janus Kinase 1) • MLL2 (Myeloid/lymphoid or mixed-lineage leukemia 2) • PMS1 (PMS1 protein homolog 1)

PTEN mutation • MSH2 mutation • MLH1 mutation • PMS1 mutation

almost3years

Microsatellite Instability and Aberrant Pre-mRNA Splicing: How Intimate Is It? (PubMed, Genes (Basel))

Because both the ATM and MRE11 genes, which as act as players in the MNR (MRE11/NBS1 (Nibrin)/RAD50 (RAD50 double strand break repair protein) DNA damage repair system, participate in double strand breaks (DSB) repair, their frequent splicing alterations in MSI cancers lead to impaired activity. This reveals the existence of a functional link between the MMR/DSB repair systems and the pre-mRNA splicing machinery, the diverted function of which is the consequence of mutations in the MS sequences.

almost 3 years ago

Journal • Microsatellite instability

MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • RAD50 (RAD50 Double Strand Break Repair Protein) • MSH3 (MutS Homolog 3) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • PMS1 (PMS1 protein homolog 1) • HSPH1 (Heat Shock Protein Family H (Hsp110) Member 1)

PMS2 mutation • MLH3 mutation • PMS1 mutation

almost3years

Association of Reported Candidate Monogenic Genes With Lung Cancer Risk. (PubMed, Clin Lung Cancer)

This study provides statistical evidence for association of previously reported genes and lung cancer risk and has clinical utility for risk assessment and genetic counseling.

almost 3 years ago

Journal • BRCA Biomarker

TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • MSH6 (MutS homolog 6) • 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) • PMS1 (PMS1 protein homolog 1) • FANCD2 (FA Complementation Group D2)

PMS1 mutation • RAD51 mutation

almost3years

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

P1/2, N=58, Active, not recruiting, Asan Medical Center | Unknown status --> Active, not recruiting | Trial completion date: Jun 2021 --> Jun 2023 | Trial primary completion date: Jun 2021 --> Jun 2023

almost 3 years ago

Enrollment closed • Trial completion date • Trial primary completion date • Metastases

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-actl)

almost3years

Analysis of Concordance Between NGS-MSI and IHC-MMR from 180,000 Solid Tumors (USCAP 2023)

Analysis of 180,000 tumors revealed a high concordance of IHC-MMR/NGS-MSI with a rate of 99.7%. In 20% of MMRp/MSI-H cases, interpretation of IHC lead to misdiagnosis that the NGS-MSI would have avoided. Clinical outcome from a large cohort of patients show NGS is not inferior compared to IHC in identifying patients with MSI-H/MMRd.

almost 3 years ago

MSi-H Biomarker • IO biomarker • Next-generation sequencing • Discordant

MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • MSH3 (MutS Homolog 3) • PMS1 (PMS1 protein homolog 1)

MSI-H/dMMR • MSH2 mutation • MLH1 mutation • MSH3 mutation • PMS2 mutation • MLH3 mutation • PMS1 mutation

MI Tumor Seek™

3years

Analysis of concordance between microsatellite instability by next generation sequencing (NGS-MSI) and mismatch repair deficiency by immunohistochemistry (IHC-MMR) in >28,000 colorectal tumors. (ASCO-GI 2023)

Here we report from >28,000 CRC tumors that the concordance of IHC-MMR/NGS-MSI is 99.74%. Clinical outcome from a large cohort of patients show NGS is not inferior compared to IHC in identifying patients with MSI-H/MMRd. The additional lens that NGS-MSI offers is of value in identifying CRC patients who may benefit from ICI therapy.

3 years ago

Next-generation sequencing • Mismatch repair • Microsatellite instability • MSi-H Biomarker • IO biomarker • Discordant

MSI-H/dMMR • MSH2 mutation • MLH1 mutation • MSH3 mutation • PMS2 mutation • MLH3 mutation • PMS1 mutation

3years

Prognostic Role of DNA Damage Response Genes Mutations and their Association With the Sensitivity of Olaparib in Prostate Cancer Patients. (PubMed, Cancer Control)

These results demonstrate that mutation in any DDR pathway results in a poor prognosis for PCa patients. Furthermore, mutations in ATR, BLM, and MLH1 or the expression of POLR2L, PMS1, FANCE, and other genes significantly influence Olaparib sensitivity, which may be underlying therapeutic targets in the future.

3 years ago

Journal • BRCA Biomarker • PARP Biomarker

BRCA2 (Breast cancer 2, early onset) • MLH1 (MutL homolog 1) • ATR (Ataxia telangiectasia and Rad3-related protein) • PMS1 (PMS1 protein homolog 1) • FANCE (FA Complementation Group E) • POLR2L (RNA Polymerase II, I And III Subunit L)

BLM mutation • PMS1 mutation • POLR2L expression

Lynparza (olaparib)

over3years

Mutant KRAS -Targeted Long Peptide Vaccine for Patients at High Risk of Developing Pancreatic Cancer (clinicaltrials.gov)

P1, N=25, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Not yet recruiting --> Recruiting

over 3 years ago

Enrollment open

KRAS (KRAS proto-oncogene GTPase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CD4 (CD4 Molecule) • EPCAM (Epithelial cell adhesion molecule) • PMS1 (PMS1 protein homolog 1)

KRAS mutation • PALB2 mutation • CDKN2A mutation • MLH1 mutation • PMS1 mutation

Hiltonol (poly-ICLC) • KRAS peptide vaccine

over3years

The clinical and genomic characteristics of MSI-h/dMMR lung cancer. (ASCO 2022)

We analyzed clinical and genomic characteristics of MSI-H/dMMR lung cancer for the first time. Our data showed that MSI-H/dMMR was found in 1.16% lung cancer patients and more likely to occur in squamous cell lung carcinoma. MSI-H/dMMR in lung cancer was associated with higher TMB and may well enhance anti-tumor immunity.

over 3 years ago

Clinical • Tumor Mutational Burden • MSi-H Biomarker • IO biomarker

TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • CD8 (cluster of differentiation 8) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • CD4 (CD4 Molecule) • PMS1 (PMS1 protein homolog 1)

TMB-H • MSI-H/dMMR • PMS1 mutation