Assessment of pathogenic variation in gynecologic cancer genes in a national cohort

Kotnik, Urška; Maver, Aleš; Peterlin, Borut; Lovrečić, Luca

doi:10.1038/s41598-023-32397-8

Cited by 3 publications

(2 citation statements)

References 65 publications

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“…There are several limitations of our study. The expected population burden of PALB2 PV/LPVs in the Slovenian population is 0.13% (Kotnik et al 2023). The absolute number of included PV/LPV carriers was small (61).…”

Section: Strengths and Limitations Of Our Studymentioning

confidence: 99%

Two recurrent pathogenic/likely pathogenic variants in PALB2 account for almost half of PALB2 positive families in Slovenia

Mesarič,

Blatnik,

Starič

et al. 2024

Preprint

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Introduction: The prevalence and spectrum of PALB2 pathogenic/likely pathogenic variants (PV/LPVs) may vary across different regions, and these have not yet been analysed and reported in Slovenian HBOC families. Methods: We performed a retrospective analysis of all 5099 consecutively tested individuals from 4610 families who fulfilled national criteria for HBOC-panel testing from January 2015 to January 2022. After genetic counselling, genetic testing with next generation sequencing was performed for all probands and cascade testing was offered to their blood relatives. Results: Among all probands tested 0.9% (40/4610) were PALB2 PV/LPV carriers. 14 different PALB2 PV/LPVs were detected, one of them was novel. Five PV/LPVs were found to be recurrent in Slovenian population with two most frequent being c.509_510del and c.1451T > A. Altogether, 61 individuals from 41 PALB2 positive families were identified, 43 being cancer patients. 27.9% PALB2-positive cancer patients were diagnosed with more than one malignant tumour. We identified three double heterozygote carriers with additional PV/LPVs in ATM, CHEK2 and BRCA1. Discussion: This report provides the first comprehensive description of molecular and clinical characteristics of PALB2 carriers in Slovenia. The frequency of PALB2 pathogenic variants in the Slovenian HBOC accounts for 0.9% of all individuals tested for PVs in HBOC-related genes. Our study adds a novel recurrent mutation, which is unique to the Slovenian context and one PV/LPVs, which had not been reported in the literature so far. The results of our study add information on genotype and phenotype in PALB2-positive patients and may be used for population specific assessment. Ethics approval: The present study was approved by the National Ethics Committee and the Institutional Ethics Committee of the Institute of Oncology Ljubljana (0120–591/2020/3 on the 20th of January 2021).

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Section: Strengths and Limitations Of Our Studymentioning

confidence: 99%

Two recurrent pathogenic/likely pathogenic variants in PALB2 account for almost half of PALB2 positive families in Slovenia

Mesarič,

Blatnik,

Starič

et al. 2024

Preprint

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“…A pathogenic gene permits a pathogen to cause disease ( Kotnik et al, 2023 ). Understanding the role of virulence genes in disease has become a central focus of medical research for the purpose of developing preventive measures, diagnostic tools, treatment approaches, and therapeutic strategies ( Jonas et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

GEO dataset mining analysis reveals novel Staphylococcus aureus virulence gene regulatory networks and diagnostic targets in mice

Xu,

Yang,

Lin

et al. 2024

Front. Mol. Biosci.

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Staphylococcus (S.) aureus infection is a serious, worldwide health concern, particularly in many communities and hospitals. Understanding the S. aureus pathogenetic regulatory network will provide significant insights into diagnostic target screening to improve clinical treatment of diseases caused by S. aureus. We screened differentially expressed genes between normal mice and S. aureus-infected mice. We used the Gene Expression Omnibus (GEO) DataSets database for functional analysis (GO-analysis) and the DAVID and KEGG databases for signaling pathway analyses. We next integrated the gene and pathway analyses with Transcriptional Regulatory Element Database (TRED) to build an antimicrobial resistance gene regulatory network of S. aureus. We performed association analysis of network genes and diseases using DAVID online annotation tools. We identified a total of 437 virulence genes and 15 transcription factors (TFs), as well as 444 corresponding target genes, in the S. aureus TF regulatory network. We screened seven key network nodes (Met, Mmp13, Il12b, Il4, Tnf, Ptgs2, and Ctsl), four key transcription factors (Jun, C3, Spil, and Il6) and an important signaling pathway (TNF). We hypothesized that the cytokine activity and growth factor activity of S. aureus are combinatorically cross-regulated by Met, Mmp13, Il12b, Il4, Tnf, Ptgs2, and Ctsl genes, the TFs Jun, C3, Spi1, and Il6, as well as the immune response, cellular response to lipopolysaccharide, and inflammatory response. Our study provides information and reference values for the molecular understanding of the S. aureus pathogenetic gene regulatory network.

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Two recurrent pathogenic/likely pathogenic variants in PALB2 account for half of PALB2 positive families in Slovenia

Mesarič,

Blatnik,

Starič

et al. 2024

Hum Genomics

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Assessment of pathogenic variation in gynecologic cancer genes in a national cohort

Cited by 3 publications

References 65 publications

Two recurrent pathogenic/likely pathogenic variants in PALB2 account for almost half of PALB2 positive families in Slovenia

Two recurrent pathogenic/likely pathogenic variants in PALB2 account for almost half of PALB2 positive families in Slovenia

GEO dataset mining analysis reveals novel Staphylococcus aureus virulence gene regulatory networks and diagnostic targets in mice

Two recurrent pathogenic/likely pathogenic variants in PALB2 account for half of PALB2 positive families in Slovenia

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