Structural analysis of genetic variants of the human tumor suppressor Palb2 coiled-coil domain.

The tumor suppressor PALB2 is a key player in the Homologous Recombination (HR) pathway, functionally connecting BRCA proteins at the DNA damage site. PALB2 forms homodimers via its coiled-coil domain, and during HR, it forms a heterodimeric complex with BRCA1 using the same domain. However, the structural details of the human PALB2 coiled-coil domain are unknown.

Case report: Achieving significant tumor reduction in advanced pancreatic adenocarcinoma.

Pancreatic cancer remains a highly malignant and challenging tumor with a dismal 5-year survival rate of only 13%. The majority of patients are diagnosed at advanced stages, where surgical options are limited, and prognosis is poor. Immunotherapy, particularly PD-1 inhibitors, has shown limited success in pancreatic cancer due to its unique tumor immune microenvironment.

Genetic modulation of RNA splicing rescues BRCA2 function in mutant cells.

Variants in the hereditary cancer-associated and genes can alter RNA splicing, producing transcripts that encode internally truncated yet potentially functional proteins. However, few studies have quantitatively analyzed variant-specific splicing isoforms. Here, we investigated cells heterozygous and homozygous for the :c.

Mutation Spectrum Analysis of BRCA1/2 Genes for Hereditary Breast and Ovarian Cancer in the Indian Population.

Objective: The objective of this study was to determine the prevalence and spectrum of genetic mutations linked to inherited breast and ovary cancer (HBOC) in the Indian population, and to evaluate the correlation of BRCA mutation types, frequency, and incidence with age, gender, and personal and family history.

Methods: A retrospective cohort of 500 Indian HBOC patients, meeting NCCN criteria who underwent BRCA1/2 testing from 2017 to 2023 were shortlisted for this study. The anonymized data was retrieved from medical records.

Whole genome and transcriptome analysis of pancreatic acinar cell carcinoma elucidates mechanisms of homologous recombination deficiency and unravels novel relevant fusion events.

Pancreatic acinar cell carcinoma (PACC) is a rare pancreatic tumor with a heterogeneous clinical course and, except for radical surgery, limited treatment options. We present a comprehensive study encompassing whole-genome and RNA sequencing of 7 tumor samples from 3 metastatic PACC patients to further delineate its genomic landscape and potential therapeutic implications. Our findings reveal distinct signatures of homologous recombination deficiency (HRD) in patients harboring pathogenic germline BRCA1/2 and FANCL mutations, demonstrating favorable responses to poly (ADP-ribose) polymerase 1 (PARP) inhibitors with prolonged disease-free intervals.