News - POLD1 mutation

16d

PolED: a manually curated database of functional studies of POLE and POLD1 variants reported in humans. (PubMed, Database (Oxford))

It also includes a concise summary of functional significance for each variant. PolED aims to assist in clinical decision-making, guide personalized therapy, and promote further research.

16 days ago

Journal • Tumor mutational burden • IO biomarker

TMB (Tumor Mutational Burden) • POLE (DNA Polymerase Epsilon) • POLD1 (DNA Polymerase Delta 1)

TMB-H • POLE mutation • POLD1 mutation

21d

The germline POLD1 c.1420 C > A (p.Leu474Ile) variant segregates with endometrial cancer, colorectal cancer and colonic polyps demonstrating hypermutation and defective POLD1 mutational signatures. (PubMed, Fam Cancer)

EC, CRC, breast and multiple polyps from three family members heterozygous for the germline POLD1 c.1420C > A variant demonstrated hypermutation and SBS10c and SBS10d TMS, genomic features associated with defective POLD1. Somatic TMB and TMS profiling of multiple independent lesions demonstrated utility for identifying POLD1-deficiency suggesting this approach can support variant classification for POLD1.

21 days ago

Journal • Tumor mutational burden

TMB (Tumor Mutational Burden) • POLD1 (DNA Polymerase Delta 1)

POLD1 mutation

Comprehensive multi-omics data to construct hepatocellular carcinoma pathway subtypes and classification model. (PubMed, Comput Biol Chem)

Moreover, our analysis identified six subtype-specific drugs, such as KU_55933 and Cyclophosphamide, that were more sensitive to PS1. In conclusion, this study successfully constructed and evaluated a pathway-based molecular subtype and classification model for HCC, thoroughly investigated the biological and multi-omics differences between subtypes. Additionally, the identification of three telomere-associated biomarkers offers guidance and a theoretical basis for personalized treatment and clinical use of drugs for HCC patients.

1 month ago

Journal

POLD1 (DNA Polymerase Delta 1) • TERF1 (Telomeric Repeat Binding Factor 1)

POLD1 mutation

cyclophosphamide • KU-55933

3ms

Defying the Prognostic Odds: A Case Report of Unexpected Complete Remission of Metastatic Ampullary Carcinoma With Palliative Chemotherapy. (PubMed, Case Rep Oncol Med)

We present a remarkable case of a 69-year-old male with Stage IV pancreaticobiliary-type AC who achieved a complete remission after 45 months of palliative modified FOLFIRINOX chemotherapy (5-fluorouracil, oxaliplatin, leucovorin, irinotecan). These findings raise questions about their potential influence on treatment response and prognosis. This case underscores the need for further investigation into the role of molecular alterations and personalized approaches in managing advanced AC.

3 months ago

Journal

PALB2 (Partner and localizer of BRCA2) • POLD1 (DNA Polymerase Delta 1) • RAD50 (RAD50 Double Strand Break Repair Protein)

PALB2 mutation • POLD1 mutation

5-fluorouracil • oxaliplatin • irinotecan • leucovorin calcium

3ms

Expressed mutated genes in Sezary syndrome and their potential prognostic value in patients treated with extracorporeal photopheresis. (PubMed, Front Immunol)

This is the first evaluation in SS of expressed mutations in a large panel of CTCL-driver genes. Also innovative is the monitoring of mutated genes in patients' malignant lymphocytes during ECP, a first-line treatment of CTCL, which highlights novel candidates associated with ECP resistance that might unmask novel pharmacological vulnerabilities to be exploited during ECP for a personalized treatment.

3 months ago

Journal

TP53 (Tumor protein P53) • ARID1A (AT-rich interaction domain 1A) • PD-1 (Programmed cell death 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • CREBBP (CREB binding protein) • POLD1 (DNA Polymerase Delta 1) • JAK3 (Janus Kinase 3) • RHOA (Ras homolog family member A) • NCOR1 (Nuclear Receptor Corepressor 1) • POT1 (Protection of telomeres 1) • TP53BP1 (Tumor Protein P53 Binding Protein 1)

TP53 mutation • ATM mutation • ARID1A mutation • TET2 mutation • POLD1 mutation

4ms

A Case of False-Negative Results in the One-Step Nucleic Acid Amplification Assay for Sentinel Lymph Node Metastasis in Breast Cancer with Low Cytokeratin 19 Expression. (PubMed, Case Rep Oncol)

False-negative results are more likely to occur for CK19-negative breast cancer, emphasizing the importance of incorporating complementary diagnostic methods, such as touch imprint cytology and different molecular markers. A multifaceted diagnostic approach is crucial for ensuring accurate staging and appropriate treatment planning.

4 months ago

Journal

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • STK11 (Serine/threonine kinase 11) • ARID1A (AT-rich interaction domain 1A) • TSC2 (TSC complex subunit 2) • FANCA (FA Complementation Group A) • POLD1 (DNA Polymerase Delta 1) • EP300 (E1A binding protein p300) • SETBP1 (SET Binding Protein 1) • KRT19 (Keratin 19)

HR positive • PIK3CA mutation • ARID1A mutation • STK11 mutation • POLD1 mutation

4ms

Predictive value of homologous recombination-related gene mutations in survival outcomes of first-line nivolumab plus chemotherapy for gastric cancer. (PubMed, Gastric Cancer)

HRR mutations were associated with favorable survival outcomes in patients treated with nivolumab plus chemotherapy. Our findings suggest that HRR mutations may serve as a potential predictive biomarker for first-line ICI-based chemotherapy in gastric cancer.

4 months ago

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

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • RAD51 (RAD51 Homolog A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • POLD1 (DNA Polymerase Delta 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • XRCC2 (X-Ray Repair Cross Complementing 2) • RAD52 (RAD52 Homolog DNA Repair Protein)

PALB2 mutation • BRIP1 mutation • RAD51C mutation • POLD1 mutation • RAD51D mutation • BARD1 mutation

Opdivo (nivolumab)

4ms

Research progress on biomarkers for proficient mismatch repair/microsatellite stable colorectal cancer in the immunotherapy era (PubMed, Zhonghua Wei Chang Wai Ke Za Zhi)

Furthermore, it addresses the challenges in the clinical application of biomarkers, such as the controversy over TMB cutoff values and the heterogeneity of PD-L1 expression. Finally, it outlines future research directions with the aim of providing a basis for clinical decision-making in immunotherapy and facilitating the realization of precision medicine.

4 months ago

Review • Journal • Mismatch repair • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker • pMMR

PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • POLD1 (DNA Polymerase Delta 1)

PD-L1 expression • POLE mutation • POLD1 mutation

4ms

Genomic landscape and molecular evolutionary trajectories of renal epithelioid angiomyolipoma and benign angiomyolipoma. (PubMed, Neoplasia)

Importantly, lower TSC2/POLDIP2 expression also predicted superior response rates to Everolimus therapy. In conclusion, our study comprehensively delineates genomic distinctions and evolutionary trajectories among renal AML subtypes, establishing TSC2, POLDIP2, NEFH, and MUC2 as prognostic biomarkers and therapeutic predictors, facilitating precision medicine in eAML management.

4 months ago

Journal

ASXL1 (ASXL Transcriptional Regulator 1) • TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1) • POLD1 (DNA Polymerase Delta 1) • MUC2 (Mucin 2) • NEFH (Neurofilament Heavy)

ASXL1 mutation • POLD1 mutation

everolimus

5ms

Comparative analysis of somatic and germline polymerase proofreading deficiencies in cancer: molecular and clinical implications. (PubMed, Mod Pathol)

In conclusion, differences between POLE and POLD1, and between somatic and germline mutations, influence clinical presentation, mutagenic potential, and reliance on cooperating defects in tumorigenesis. These insights advance the understanding of proofreading-deficient cancers, with implications for diagnostics, genetic counseling, and precision oncology.

5 months ago

Journal • Tumor mutational burden

TMB (Tumor Mutational Burden) • POLD1 (DNA Polymerase Delta 1)

TMB-H • POLD1 mutation

5ms

Beyond proofreading: POLD1 mutations as dynamic orchestrators of genomic instability and immune evasion in cancer. (PubMed, Front Immunol)

By elevating tumor mutation burden and generating unique mutational signatures (e.g., SBS10d), POLD1 mutations sensitize MSS tumors to ICIs, challenging the dominance of microsatellite instability (MSI) as an immunotherapy predictor. Integrating structural insights, molecular mechanisms, and clinical data, this review positions POLD1 mutations as both a driver of cancer progression and a promising biomarker, redefining therapeutic possibilities in precision oncology.

5 months ago

Review • Journal • Tumor mutational burden • IO biomarker

TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • POLD1 (DNA Polymerase Delta 1)

POLD1 mutation

5ms

Identification and Validation of a Previously Missed Mutational Signature in Colorectal Cancer. (PubMed, bioRxiv)

However, multiple lines of evidence, including the absence of pathogenic mutations in the exonuclease domain of POLD1 or in mismatch repair-associated genes, indicate that SBS_D is not driven by canonical defects in these DNA repair pathways. Overall, this study identifies a previously unrecognized mutational signature in microsatellite-stable CRC and proposes that its etiology may be linked to DNA repair infidelity emerging late in tumor development in samples without canonical defects in DNA repair pathways.

5 months ago

Journal

POLD1 (DNA Polymerase Delta 1)

POLD1 mutation