POLD1 mutation

P2, N=21, Active, not recruiting, Rutgers, The State University of New Jersey | Recruiting --> Active, not recruiting | N=40 --> 21 | Trial completion date: Oct 2023 --> Sep 2027

These molecular tools have the potential to change how CRC is managed by earlier detection and more precise predictive biomarkers. However, large-scale validation and clinical standardization are still crucial for their extensive utilization.

Integrating multiple biomarkers may provide superior stratification and guide therapeutic strategies. Prospective validation and standardized biomarker assessment will be imperative to translate these insights into clinical practice.

P2, N=197, Recruiting, Gruppo Oncologico del Nord-Ovest | N=140 --> 197

Benign struma ovarii do not harbor BRAF alterations. DICER1 and POLD1 variants need further investigation in this tumor pathology.

Postoperatively, the patient received 4 cycles of XELOX chemotherapy plus nivolumab, followed by consolidative radiotherapy synchronized with capecitabine and nivolumab, and subsequent maintenance therapy with capecitabine and nivolumab until sustained no evidence of disease (NED) was confirmed in January 2023. This exceptional and sustained response may be attributed to the synergistic effect of TMB-H and POLD1 mutation, which enhance neoantigen generation and sensitize tumors to immunotherapy. This case highlights the potential of biomarker-driven chemo-immunotherapy combined with MDT-guided multimodal treatment (surgery + adjuvant therapy + consolidative radiotherapy) to achieve curative intent in patients with metastatic GMC, providing valuable insights for personalized treatment strategies in this poor-prognosis population.

MMR and p53 IHC serve as practical frontline tools, while POLE sequencing should be prioritized for intermediate- and high-risk endometrioid tumors. Expanded molecular testing in Asian populations is essential to refine risk stratification and optimize individualized management.

The most frequently mutated gene is NOTCH1. Extensive fusion gene, expression and molecular cluster analyses provide a molecular portrait of this rare and enigmatic tumour type.

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.

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.

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.

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.