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MUTYH (MutY homolog)

News alerts, weekly reports and conference planners

Mismatch Repair (MMR) and Homologous Recombination (HR) Deficiency: Real-Life Applications of biomarkers for complementary approaches in Epithelial Ovarian Cancer (AIOM 2024)

HRD genomic instability tests and multigene panel assessments serve as synergistic tools in EOC clinical settings, proving essential for identifying patients likely to benefit from PARPi therapy. These tools also enhance the detection of HRR and MMR gene variants, aiding in preventive care. Further investigations into the genetic profiles of HRD-negative tumors are crucial for advancing cancer risk management and developing novel therapeutic avenues.

6 days ago

Clinical • Mismatch repair • BRCA Biomarker • PARP Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MLH1 (MutL homolog 1) • PMS2 (PMS1 protein homolog 2) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • MUTYH (MutY homolog)

BRCA2 mutation • BRCA1 mutation • HRD • BRCA wild-type

Myriad myChoice® CDx

Germline pathogenic variants in prostate cancer. (PubMed, Pathol Res Pract)

Individuals with a family history of cancer were significantly more likely to have a pathogenic or likely pathogenic variant than those without one (p = 0.002). Overall, our results show the necessity for future research with a larger sample size to better explain the relationship between clinicopathologic data and genetic variants.

6 days ago

Journal • BRCA Biomarker

TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • MUTYH (MutY homolog) • HOXB13 (Homeobox B13) • LZTR1 (Leucine Zipper Like Transcription Regulator 1)

APEX1 Polymorphisms Affect Acute Myeloid Leukemia Risk, and Its Expression Is Involved in Cell Proliferation and Differentiation. (PubMed, Int J Lab Hematol)

In the GSE48558 dataset, AML cells and normal CD34+ cells expressed APEX1 at higher levels than did granulocytes (p < 0.01). Functional experiments revealed that APEX1 knockdown led to a reduction in AML cell proliferation. These findings indicated that APEX1 polymorphisms were a potential risk factor for AML and highlighted the important role of APEX1 in regulating AML cell differentiation and proliferation.

7 days ago

Journal

CD34 (CD34 molecule) • MUTYH (MutY homolog) • XRCC1 (X-Ray Repair Cross Complementing 1) • APEX1 (Apurinic/Apyrimidinic Endodeoxyribonuclease 1)

Clinical Assessment and Genetic Testing for Hereditary Polyposis Syndromes in an Italian Cohort of Patients with Colorectal Polyps. (PubMed, Cancers (Basel))

Our findings indicate that stringent NCCN eligibility criteria for molecular screening may lead to missing some of the patients affected by hereditary polyposis syndromes. This highlights the need for a careful evaluation of patients' clinical manifestations, polyp number, age of polyp onset, and family history to select appropriate candidates for molecular diagnosis of these conditions.

8 days ago

Journal

PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • SMAD4 (SMAD family member 4) • APC (APC Regulator Of WNT Signaling Pathway) • MUTYH (MutY homolog) • BMPR1A (Bone Morphogenetic Protein Receptor Type 1A)

16d

Prospective germline sequencing of patients with gliomas, glioneuronal or neuronal tumors (SNO 2024)

Clinical germline sequencing identifies a germline mutation in a high proportion of patients with CNS tumors. Biallelic inactivation was most commonly identified in tumors from patients with germline TP53 or NF1 mutations and were less common in patients with a germline MMR alteration.

16 days ago

Clinical • BRCA Biomarker

TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NF1 (Neurofibromin 1) • CHEK2 (Checkpoint kinase 2) • MUTYH (MutY homolog)

TP53 mutation • NF1 mutation • CHEK2 mutation • IDH wild-type

MSK-IMPACT

18d

Carrier Frequency and Incidence of MUTYH-Associated Polyposis Based on Database Analysis in East Asians and Koreans. (PubMed, Ann Lab Med)

This was the first study to investigate the frequency of carriers of MUTYH-associated polyposis in East Asians, including specific subgroups, utilizing gnomAD and a Korean genome database. Our data provide valuable reference information for future investigations of MUTYH-associated polyposis to understand the genetic diversity and specific variants associated with this condition in East Asian populations.

18 days ago

Journal

MUTYH (MutY homolog)

27d

Two Decades of Progress in Personalized Medicine of Colorectal Cancer in Serbia-Insights from the Institute for Oncology and Radiology of Serbia. (PubMed, Biomedicines)

Although significant improvements in CRC management have occurred globally in recent years, a strategic approach leading to population-based systemic solutions is required. The high incidence of young-onset CRC and the growing elderly population due to a rise in life expectancy will be especially important factors for countries with limited healthcare resources like Serbia.

27 days ago

Journal

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • APC (APC Regulator Of WNT Signaling Pathway) • RAS (Rat Sarcoma Virus) • CHEK2 (Checkpoint kinase 2) • MUTYH (MutY homolog)

KRAS mutation • BRAF mutation • NRAS mutation • BRAF V600 • RAS mutation • CHEK2 mutation

29d

Comparative targeted genome profiling between solid and liquid biopsies in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs): a proof-of-concept pilot study. (PubMed, Neuroendocrinology)

This pilot study explores the applicability of LB in GEP-NETs MP evaluation. Further studies with larger cohorts are needed to validate LB and to define the clinical impact.

29 days ago

Journal • Liquid biopsy • Tumor mutational burden • Biopsy

TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • mTOR (Mechanistic target of rapamycin kinase) • ATRX (ATRX Chromatin Remodeler) • TSC2 (TSC complex subunit 2) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • MUTYH (MutY homolog) • DAXX (Death-domain associated protein) • DEPDC5 (DEP Domain Containing 5, GATOR1 Subcomplex Subunit) • MEN1 (Menin 1)

PTEN mutation • ARID1A mutation • TSC2 mutation • MTOR mutation

Germline DNA Damage Repair Gene Alterations in Patients with Metachronous Breast and Colorectal Cancer. (PubMed, Int J Mol Sci)

A significant fraction of BC/CRC patients with a family history of these tumors harbored deleterious germline variants in DNA repair genes. Our findings can lead to strategies to improve the diagnosis, genetic counseling, and treatment of patients and their relatives.

1 month ago

Journal

MLH1 (MutL homolog 1) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • MUTYH (MutY homolog) • MAD1L1 (Mitotic Arrest Deficient 1 Like 1) • NOS3 (Nitric oxide synthase 3) • LAMA1 (Laminin Subunit Alpha 1) • PABPC1 (Poly(A) Binding Protein Cytoplasmic 1)

A maternal germline mutator phenotype in a family affected by heritable colorectal cancer. (PubMed, Genetics)

Surprisingly, we detect no significant elevation of the C>A mutation rate in children born to a father with the same MUTYH genotype, and we similarly find that the mutator effect of the mouse homolog Mutyh appears to be localized to embryonic development, not the spermatocytes. Our results suggest that maternal MUTYH variants can cause germline mutations by attenuating the repair of oxidative DNA damage in the early embryo.

1 month ago

Journal

MUTYH (MutY homolog)

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.

1 month ago

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)

2ms

The Adrenal Pheochromocytoma Cell Line PC12 Efficiently Promotes the Regeneration Capability of Adipose Tissue-Derived Mesenchymal Stem Cells in Myogenesis: A Particular Approach to Improving Skeletal Muscle Cell Regeneration. (PubMed, Iran J Med Sci)

Differentiation of ADSCs was induced by using 3 μg/mL 5-azacytidine for 24 hours...Coculturing PC12 cells and ADSCs improves the efficiency of myogenic differentiation. However, the effectiveness of myogenic differentiation depends on the proportions of administered PC12 cells.

2 months ago

Preclinical • Journal

MUTYH (MutY homolog)

azacitidine

2ms

Synchronous Seminoma of Testis and Renal Cell Carcinoma: A Rare Case Report. (PubMed, Medicina (Kaunas))

Chemotherapy with a Bleomycin, Etoposide, and Cisplatin (BEP) regimen was carried out...Treatment with targeted therapy with Sunitinib was started because the risk was favourable according to the Heng criteria... According to the authors, the occurrence of synchronous primary tumours is linked to one's genetic predisposition. DNA sequencing of tumour tissue could provide more information on the corresponding aetiopathogenesis.

2 months ago

Journal

STK11 (Serine/threonine kinase 11) • BAP1 (BRCA1 Associated Protein 1) • CHEK2 (Checkpoint kinase 2) • MUTYH (MutY homolog)

cisplatin • sunitinib • etoposide IV • bleomycin

2ms

Glucagon-Producing Pancreatic Neuroendocrine Tumors (Glucagonomas) are Enriched in Aggressive Neoplasms with ARX and PDX1 Co-expression, DAXX/ATRX Mutations, and ALT (Alternative Lengthening of Telomeres). (PubMed, Endocr Pathol)

During follow-up, one patient died of the disease, and four patients developed distant metastasis. Pancreatic glucagonomas are distinct PanNETs with specific clinicopathological and molecular features, including histological aspects of biological aggressiveness, co-occurring alpha- and beta-cell differentiation, MEN1 and DAXX/ATRX mutations enrichment, and the possible presence of high-TMB as an actionable marker.

2 months ago

Journal • Tumor mutational burden

TMB (Tumor Mutational Burden) • ATRX (ATRX Chromatin Remodeler) • MUTYH (MutY homolog) • DAXX (Death-domain associated protein) • PDX1 (Pancreatic And Duodenal Homeobox 1) • SYP (Synaptophysin)

TMB-H • ATRX mutation

2ms

Prevalence and spectrum of germline pathogenic variants in cancer susceptibility genes among mexican patients with exocrine pancreatic cancer. (PubMed, Pancreatology)

We identified a significant frequency of actionable germline PVs in Mexicans with PC, wherein the majority were in a broad spectrum of genes associated with the homologous recombination DNA repair mechanism. Most pancreatic cancer associated PVs were detected in non-BRCA genes, so our findings support the recommendation of multigene panel testing for genetic cancer risk assessment of Mexican individuals with PC.

2 months ago

Journal • BRCA Biomarker

TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • MUTYH (MutY homolog)

2ms

Clinical characteristics and genomic profiling of outpatients with endometrial cancer at a Chinese tertiary cancer center. (PubMed, Discov Oncol)

Outpatients department gathered a considerable proportion of recurrent patients with complex genomic features. Patients with worse prognosis could be well studied, and anti-PD1 therapy was a promising salvage therapy in the real world.

2 months ago

Journal • BRCA Biomarker • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker

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) • FANCA (FA Complementation Group A) • RAD50 (RAD50 Double Strand Break Repair Protein) • MUTYH (MutY homolog)

BRCA2 mutation • BRCA1 mutation • MSI-H/dMMR • MSH2 mutation • FANCA mutation • MLH1 mutation • RAD50 mutation

2ms

Prevalence of germline variants in Brazilian pancreatic carcinoma patients. (PubMed, Sci Rep)

Therefore, genetic testing should be offered to all Brazilian pancreatic cancer patients, regardless of their ancestry. Genes with limited or previously unrecognized associations with pancreatic cancer should be further investigated to clarify their role in cancer risk.

2 months ago

Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PALB2 (Partner and localizer of BRCA2) • MSH2 (MutS Homolog 2) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • MRE11A (MRE11 homolog, double strand break repair nuclease) • MUTYH (MutY homolog) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • FANCM (FA Complementation Group M) • FANCE (FA Complementation Group E) • MITF (Melanocyte Inducing Transcription Factor) • RECQL4( RecQ Like Helicase 4) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)

3ms

Infiltrating Ductal Breast Carcinoma in a Male Patient With Associated BARD1 Mutation. (PubMed, Cureus)

Genetic testing of the excised tumor revealed a MUTYH gene mutation and a BARD1 (BRCA1-associated RING domain 1) gene mutation of unknown significance. Histopathological analysis confirmed a Grade 2, ER/PR-positive, KI 67-positive, and HER2-negative tumor.

3 months ago

Journal • BRCA Biomarker

HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BARD1 (BRCA1 Associated RING Domain 1) • MUTYH (MutY homolog)

BRCA1 mutation • HER-2 negative • ER positive + PGR positive • BARD1 mutation • HER-2 negative + AR positive + ER positive • HER-2 negative + PGR positive

3ms

Comprehensive exploration on the role of base excision repair genes in modulating immune infiltration in low-grade glioma. (PubMed, Pathol Res Pract)

Our findings suggest that the BER genes MUTYH, PNKP, UNG and XRCC1 can potentially be prognostic biomarkers and highly correlate with the immune cells of the tumour microenvironment.

3 months ago

Journal • PD(L)-1 Biomarker • IO biomarker

IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • MUTYH (MutY homolog) • XRCC1 (X-Ray Repair Cross Complementing 1)

3ms

Frequency of Deleterious Germline Variants in HER2-Low Breast Cancer Patients Using a Hereditary Multipanel Gene Testing. (PubMed, Curr Issues Mol Biol)

Similar alterations in BRCA were observed in this group of patients compared to the overall cohort. Germline genetic tests should be evaluated in larger cohorts of patients with HER2-Low status to better address the findings.

3 months ago

Journal • 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) • MLH1 (MutL homolog 1) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • MERTK (MER Proto-Oncogene, Tyrosine Kinase) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • MUTYH (MutY homolog) • RECQL4( RecQ Like Helicase 4)

3ms

Unraveling druggable cancer-driving proteins and targeted drugs using artificial intelligence and multi-omics analyses. (PubMed, Sci Rep)

This strategy effectively predicts and prioritizes biomarkers, therapeutic targets, and drugs for in-depth studies in clinical trials. Scripts are available at https://github.com/muntisa/machine-learning-for-druggable-proteins .

3 months ago

Journal

HRAS (Harvey rat sarcoma viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • CCNE1 (Cyclin E1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • TSC1 (TSC complex subunit 1) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • PREX2 (Phosphatidylinositol-3,4,5-Trisphosphate Dependent Rac Exchange Factor 2) • ACVR1 (Activin A Receptor Type 1) • CASP8 (Caspase 8) • MUTYH (MutY homolog) • CDKN2C (Cyclin Dependent Kinase Inhibitor 2C) • JAG1 (Jagged Canonical Notch Ligand 1) • VAV1 (Vav Guanine Nucleotide Exchange Factor 1) • ATG7 (Autophagy Related 7) • BUB1B (BUB1 Mitotic Checkpoint Serine/Threonine Kinase B) • PPP2R1A (Protein Phosphatase 2 Scaffold Subunit Aalpha)

3ms

Adenomas from individuals with pathogenic biallelic variants in the MUTYH and NTHL1 genes demonstrate base excision repair tumour mutational signature profiles similar to colorectal cancers, expanding potential diagnostic and variant classification applications. (PubMed, medRxiv)

SBS18+SBS36 and SBS30 were enriched in adenomas at comparable proportions observed in CRCs from biallelic MUTYH and biallelic NTHL1 cases, respectively. Therefore, testing adenomas may improve the identification of biallelic cases and facilitate variant classification, ultimately enabling opportunities for CRC prevention.

3 months ago

Journal

MUTYH (MutY homolog)

4ms

Hereditary Colorectal Cancer and Polyposis Syndromes Caused by Variants in Uncommon Genes. (PubMed, Genes Chromosomes Cancer)

PV/LPV in these uncommon gene can be responsible for up to 2.7% of inherited CRC or colonic polyposis syndromes. Our findings provide supporting evidence for the role of these genes in cancer predisposition, and contribute to the determination of related cancer spectrum and cancer risk for carriers, allowing for the establishment of appropriate screening strategy and genetic counseling in affected families.

4 months ago

Journal

TP53 (Tumor protein P53) • RNF43 (Ring Finger Protein 43) • APC (APC Regulator Of WNT Signaling Pathway) • MUTYH (MutY homolog) • BUB1 (BUB1 Mitotic Checkpoint Serine/Threonine Kinase)

4ms

SMARCA4-Deficient Colonic Tumor in a Patient with mutY DNA Glycosylase (MUTYH) Associated Polyposis. (PubMed, Am Surg)

No abstract available

4 months ago

Journal

SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • MUTYH (MutY homolog)

4ms

Patterns and Frequency of Pathogenic Germline Mutations among Patients with Newly-Diagnosed Endometrial Cancer: The Jordanian Exploratory Cancer Genetics (Jo-ECAG) Endometrial Study. (PubMed, Cancers (Basel))

P/LP variants were more common among patients with carcinosarcoma and clear cell carcinoma, younger patients (age ≤ 50 years), and in patients with a non-metastatic disease. We conclude that germline genetic variants, mostly in genes related to the Lynch syndrome, are relatively common among Arab patients with endometrial cancer.

4 months ago

Journal • BRCA Biomarker

BRCA2 (Breast cancer 2, early onset) • MLH1 (MutL homolog 1) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • APC (APC Regulator Of WNT Signaling Pathway) • MUTYH (MutY homolog)

4ms

Germline variants in patients diagnosed with pediatric soft tissue sarcoma. (PubMed, Acta Oncol)

A high fraction of young patients with soft tissue sarcoma harbor PVs. Among the genes affected, we substantiate a potential role of MYO5B and propose a potential role for MYO3A.

4 months ago

Retrospective data • Journal

TP53 (Tumor protein P53) • FANCA (FA Complementation Group A) • MUTYH (MutY homolog) • DICER1 (Dicer 1 Ribonuclease III) • FANCC (FA Complementation Group C)

4ms

Germline Sequencing of DNA Damage Repair Genes in Two Hereditary Prostate Cancer Cohorts Reveals New Disease Risk-Associated Gene Variants. (PubMed, Cancers (Basel))

Evaluation of clinicopathological characteristics provided no evidence for a younger age or higher-grade disease at diagnosis in variant carriers, which should be taken into consideration when determining genetic screening eligibility criteria for targeted, gene-based treatments in the future. This study adds valuable knowledge to our understanding of PrCa-associated DDR genes, which will underpin effective clinical screening and treatment strategies.

4 months ago

Journal • PARP Biomarker

BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • MUTYH (MutY homolog) • ERCC3 (ERCC Excision Repair 3, TFIIH Core Complex Helicase Subunit) • PARP2 (Poly(ADP-Ribose) Polymerase 2)

5ms

Endometrial serous carcinoma with a corded and hyalinized pattern: a clinicopathological and molecular analysis. (PubMed, Pathologica)

The patient had a recurrence on the vaginal stump after 15 months. In conclusion, endometrial serous carcinoma can show a corded and hyalinized pattern, which may represent a diagnostic challenge.

5 months ago

Journal

PGR (Progesterone receptor) • MLH1 (MutL homolog 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • PMS2 (PMS1 protein homolog 2) • WT1 (WT1 Transcription Factor) • APC (APC Regulator Of WNT Signaling Pathway) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • POLD1 (DNA Polymerase Delta 1) • EPCAM (Epithelial cell adhesion molecule) • MUTYH (MutY homolog) • GATA3 (GATA binding protein 3)

5ms

Attenuated adenomatous polyposis with MSH6 variation: Two case reports. (PubMed, Medicine (Baltimore))

Minor portion of AAP can cause by genetic mutation in MSH6, and further research is needed.

5 months ago

Journal

MSH6 (MutS homolog 6) • MUTYH (MutY homolog)

5ms

Synchronous Endometrial and Ovarian Endometrioid Carcinoma With MUTYH Germline Mutation: A Case Report With Genetic Analysis. (PubMed, Int J Gynecol Pathol)

She is being followed periodically and is normal 15 months after surgery. To the best of our knowledge, this study presents the first case of a patient with synchronous endometrial and ovarian endometrioid carcinoma harboring a monoallelic pathogenic MUTYH germline variant.

5 months ago

Journal

MUTYH (MutY homolog)

5ms

Spectrum of germline pathogenic variants in Brazilian hereditary breast/ovarian cancer cases. (PubMed, Breast Cancer Res Treat)

The rate of PVs detected in high-risk individuals in this study was twice the 10% threshold used in Brazilian health guidelines. MGPT doubled the detection rate of PVs in cancer susceptibility genes in high-risk individuals compared with BRCA1/BRCA2 genotyping alone. The spectrum of PVs in Southern Brazil is diverse, with few recurring variants such as TP53 (0.6%), suggesting regional founder effects. The use of MGPT in hereditary cancer in Minas Gerais significantly increased the detection rate of P/LPVs compared to existing guidelines and should be considered as the primary genotyping modality in assessing hereditary cancer risk in Brazil.

5 months ago

Journal • BRCA Biomarker

TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MUTYH (MutY homolog)

5ms

Well-differentiated G1 and G2 pancreatic neuroendocrine tumors: a meta-analysis of published expanded DNA sequencing data. (PubMed, Front Endocrinol (Lausanne))

Increased understanding of the genetic alterations may lead to identification of more drivers and driver hotspots in the tumorigenesis in well-differentiated PNETs, potentially giving a basis for the identification of new drug targets. (Funded by Novo Nordisk Foundation, grant number NNF19OC0057915).

5 months ago

Clinical • Retrospective data • Review • Journal • BRCA Biomarker

BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • MUTYH (MutY homolog) • CDKN1B (Cyclin dependent kinase inhibitor 1B) • DAXX (Death-domain associated protein) • MEN1 (Menin 1)

6ms

Carrier testing for partners of MUTYH variant carriers: UK Cancer Genetics Group recommendations. (PubMed, J Med Genet)

No abstract available

6 months ago

Journal

MUTYH (MutY homolog)

6ms

Exploring the Role of the MUTYH Gene in Breast, Ovarian and Endometrial Cancer. (PubMed, Genes (Basel))

our results fail to demonstrate that germinal monoallelic MUTYH variants increase cancer risk through a LOH (loss of heterozygosity) mechanism in the somatic tissue; however, the absence or partial loss of the MUTYH protein in many tumors suggests its dysregulation regardless of MUTYH genetic status.

6 months ago

Journal

MUTYH (MutY homolog)

6ms

Chemotherapy-free treatment targeting fusions and driver mutations in KRAS wild-type pancreatic ductal adenocarcinoma, a case series. (PubMed, Ther Adv Med Oncol)

Five patients were treated with matched targeted therapy, with three having durable benefit: (i) erlotinib for EGFR-altered tumor, followed by osimertinib/capmatinib when MET amplification emerged (first-line therapy); (ii) pralsetinib for RET fusion (fifth line); and (iii) dabrafenib/trametinib for BRAF N486_P490del (third line). Sustained therapeutic benefit can be achieved in a real-world setting in a subset of patients with advanced/metastatic KRAS-WT PDAC treated with chemotherapy-free matched targeted agents. Prospective studies are warranted.

6 months ago

Journal

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • FGFR2 (Fibroblast growth factor receptor 2) • STK11 (Serine/threonine kinase 11) • MUTYH (MutY homolog) • PCM1 (Pericentriolar Material 1) • POC1B (POC1 Centriolar Protein B)

KRAS mutation • MET amplification • RET fusion • KRAS wild-type • FGFR2 fusion • RAS wild-type • EGFR E746

Mekinist (trametinib) • Tagrisso (osimertinib) • erlotinib • Tafinlar (dabrafenib) • Gavreto (pralsetinib) • Tabrecta (capmatinib)

7ms

Updated European guidelines for clinical management of familial adenomatous polyposis (FAP), MUTYH-associated polyposis (MAP), gastric adenocarcinoma, proximal polyposis of the stomach (GAPPS) and other rare adenomatous polyposis syndromes: a joint EHTG-ESCP revision. (PubMed, Br J Surg)

These updated guidelines provide current, comprehensive, and evidence-based practical recommendations for the management of surveillance and treatment of familial adenomatous polyposis patients, encompassing additionally MUTYH-associated polyposis, gastric adenocarcinoma and proximal polyposis of the stomach and other recently identified polyposis syndromes based on pathogenic variants in other genes than APC or MUTYH. Due to the rarity of these diseases, patients should be managed at specialized centres.

7 months ago

Clinical guideline • Review • Journal

MUTYH (MutY homolog)

7ms

A comprehensive characterization of the spectrum of MUTYH germline pathogenic variants in Latin America. (PubMed, Fam Cancer)

We reported a high frequency of European founder variants in our diverse population. Some phenotypic differences from current studies were identified, such as a higher breast cancer burden in monoallelic carriers and a complete absence of extra-colon tumors in biallelic patients.

7 months ago

Journal

MUTYH (MutY homolog)

7ms

Associations between pathological features and risk of metachronous colorectal cancer. (PubMed, Int J Cancer)

Compared to cases who had an adenocarcinoma histologic type, those with an undifferentiated histologic type were 77% less likely to develop a metachronous CRC (adjusted HR: 0.23, 95% CI: 0.06-0.94). Existing surveillance guidelines for CRC survivors could be updated to include increased surveillance for those whose first CRC was diagnosed with a synchronous CRC or was MMR-deficient.

7 months ago

Journal

MUTYH (MutY homolog)

7ms

Characterization of DNA damage repair (DDR) alterations and the tumor immune microenvironment (TIME) in advanced non-small cell lung cancer (NSCLC). (ASCO 2024)

In this large, real-world cohort of pts with metastatic NSCLC, DDRmt was associated with distinct TIME patterns including high TMB, MSI-H, and modest changes in immune cell infiltrates. These findings warrant further studies to understand how DDR pathway alterations mediate changes in the TIME to inform novel combinatorial immunotherapeutic approaches in NSCLC.

7 months ago

Tumor mutational burden • PD(L)-1 Biomarker • PARP Biomarker • MSi-H Biomarker • BRCA Biomarker • IO biomarker • Metastases

PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • PMS2 (PMS1 protein homolog 2) • MUTYH (MutY homolog) • ERCC3 (ERCC Excision Repair 3, TFIIH Core Complex Helicase Subunit)

Tempus xT Assay • Tempus xR

7ms

Germline and somatic MUTYH mutations: Clinicopathologic and mutational analysis in a pan-cancer cohort. (ASCO 2024)

This study represents the largest cohort of pts with MUTYH gPVs and FACETS analysis on concurrent tumor samples, confirming a high prevalence of LOH in pts with monoallelic MUTYH gPVs and enrichment in KRAS G12Cin pts with MUTYH gPVs and biallelic MUTYH inactivation.

7 months ago

Clinical • BRCA Biomarker • Pan tumor

KRAS (KRAS proto-oncogene GTPase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • MUTYH (MutY homolog)

MSK-IMPACT

7ms

Curative resection via right hemicolectomy and regional lymph node dissection for colonic adenomatous polyposis of unknown etiology with adenocarcinomas localized in the right side of the colon: a case report. (PubMed, Surg Case Rep)

In this rare case, colonic adenomatous polyposis of unknown etiology, with numerous adenomatous polyps and multiple adenocarcinomas localized in the right side of the colon, was successfully treated with right hemicolectomy and regional lymph node dissection. Despite genetic analysis, no causative germline variants were identified. Segmental colectomy according to the distribution of polyps might be a curative approach.

7 months ago

Journal

TP53 (Tumor protein P53) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • POLD1 (DNA Polymerase Delta 1) • EPCAM (Epithelial cell adhesion molecule) • MBD4 (Methyl-CpG Binding Domain 4, DNA Glycosylase) • MSH3 (MutS Homolog 3) • MUTYH (MutY homolog)

7ms

Targeted genotyping for recurring variants in cancer susceptibility genes in non-Ashkenazi Jewish patients with breast cancer diagnosed ≥50 years. (PubMed, Cancer)

The observed low rates of PV detection in non-AJ non-TNBC cases ≥age 50 years at diagnosis, mostly for clinically insignificant variants, questions the justification of unselected genotyping in this subset of patients.

7 months ago

Journal

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PMS2 (PMS1 protein homolog 2) • CHEK2 (Checkpoint kinase 2) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • MUTYH (MutY homolog)