Publications by authors named "Carolyn Paisie"
Article Synopsis
- * It achieves a high level of completeness, closing 92% of previous assembly gaps and fully assembling complex regions, including 1,852 complex structural variants and 1,246 human centromeres.
- * The findings lead to significant improvements in genotyping accuracy and enable the detection of over 26,000 structural variants per sample, enhancing the potential for future disease association research.
Article Synopsis
- Outbred laboratory mice (Mus musculus) are popular in biomedical research due to their high reproduction rates and availability, and high throughput genome sequencing (HTS) helps ensure the genetic quality and reproducibility of studies using these mice.
- A study on a newly established Swiss-derived outbred population (J:ARC) utilized exome sequencing to explore their genetic architecture and found characteristics typical of well-maintained outbred stocks, comparing it to the Diversity Outbred (J:DO) stock.
- The J:DO stock showed greater genetic variation and interindividual variability but had a higher frequency of potentially damaging genetic variants, indicating that diverse genetic backgrounds can help buffer against harmful mutations under varying selective pressures.
Article Synopsis
- Patient-derived xenograft (PDX) models offer a valuable platform for testing new cancer drugs, specifically for lung cancer, with a repository of 79 extensively characterized models.
- The collection mainly includes non-small cell lung cancer (NSCLC) variants, such as adenocarcinoma and squamous cell carcinoma, and incorporates models that exhibit resistance to targeted therapies.
- The genomic features of the PDXs align with those in actual patient tumors, confirming their relevance for preclinical research and their ability to predict treatment responses.
Article Synopsis
- - Cancer of unknown primary (CUP) accounts for 3-5% of cancers and is defined as metastatic cancers where the primary site remains unidentified, leading to poor survival outcomes for patients who are disadvantaged in treatment options.
- - Researchers developed an RNA-based diagnostic tool called CUP-AI-Dx using a 1D Inception convolutional neural network to identify the primary tissue origin of tumors, trained on extensive genetic data from various cancer types.
- - CUP-AI-Dx demonstrated high accuracy, achieving 98.54% in cross-validation and 96.70% on test datasets, confirming its potential to aid in diagnosing CUP and improving treatment strategies for affected patients.
Article Synopsis
- Cellular senescence is linked to aging and impairs tissue regeneration, contributing to neurodegenerative diseases like multiple sclerosis (MS).
- Neural progenitor cells (NPCs) from patients with primary progressive MS (PPMS) show signs of cellular senescence, which limits their ability to support the maturation of oligodendrocyte progenitor cells (OPCs).
- Treatment with rapamycin can reverse senescence in PPMS NPCs, increasing their ability to assist in oligodendrocyte differentiation, highlighting the role of cellular aging in MS and potential pathways for future treatments.
Article Synopsis
- - Leishmania infantum causes leishmaniasis in humans and dogs, with Phlebotomus perniciosus being the main sand fly vector; obtaining parasites for study from these flies is difficult, so researchers often use axenic (sterile) cultures of the parasites.
- - The study utilized Spliced Leader RNA-seq (SL-seq) to analyze and compare gene expression in cultured promastigotes versus those isolated from the sand fly's gut after infection, successfully avoiding contamination from the insect's RNA.
- - Findings revealed a moderate correlation in gene expression between the two sources, but 793 genes had notably different expression levels, indicating that sand fly-derived promastigotes may be more developed in their
Article Synopsis
- - The gene located at the fragile FRA3B locus experiences deletions due to carcinogen exposure and replication stress, leading to genome instability and promoting hypermutation.
- - Research indicates that the loss of this gene correlates with COSMIC mutational signature 5, supported by data analysis of over 6,500 cancer samples from the TCGA database.
- - Additionally, Fhit-deficient mice show mutational signatures similar to signature 5, suggesting that the loss of this gene may serve as a marker for early cancer development and can be influenced by carcinogen exposure.
Article Synopsis
- * Research on Fhit-deficient mouse models has shown a significant increase in genetic mutations, including single-base substitutions, which resembles mutation patterns found in human cancers like kidney, esophageal, and bladder cancers.
- * The mutation patterns may be linked to an imbalance in nucleotide pools due to low thymidine kinase 1 expression, alongside evidence suggesting that specific treatments can induce further mutations in Fhit-deficient cells.
Article Synopsis
- The FHIT gene is crucial for DNA protection in precancerous cells, and its fragile nature makes it susceptible to damage, which can lead to cancer.
- FHIT protein expression helps maintain genome stability and manage oxidative stress, making it an important tumor suppressor.
- Current research focuses on understanding how FHIT interacts with reactive oxygen species and DNA damage in cancer development.
Article Synopsis
- Triple negative breast cancers (TNBC) have poor survival rates and limited treatment options, with androgen receptor (AR) expression potentially playing a role in their pathology.
- In a study of 678 breast cancer cases, including 396 TNBCs, it was found that only 24.8% of TNBCs expressed AR, significantly lower than the 81.6% of non-TNBC cases, especially in African American women.
- Positive AR expression was linked to lower tumor grades and better survival outcomes in non-basal TNBCs, and gene expression analysis identified potential therapeutic targets that differ based on AR status, emphasizing the need for targeted treatments in TNBC.
Loss of Fhit expression, encoded at chromosome fragile site FRA3B, leads to increased replication stress, genome instability and accumulation of genetic alterations. We have proposed that Fhit is a genome 'caretaker' whose loss initiates genome instability in preneoplastic lesions. We have characterized allele copy number alterations and expression changes observed in Fhit-deficient cells in conjunction with alterations in cellular proliferation and exome mutations, using cells from mouse embryo fibroblasts (MEFs), mouse kidney, early and late after establishment in culture, and in response to carcinogen treatment.
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- - The study investigates why tyrosine kinase inhibitors (TKIs) are ineffective on quiescent hematopoietic stem cells (HSCs) in chronic myeloid leukemia (CML), revealing that these resistant cells rely on the suppression of the tumor suppressor protein PP2A rather than the BCR-ABL1 kinase activity.
- - CML quiescent HSCs exhibited increased BCR-ABL1 expression without its kinase activity, leading to the activation of a survival pathway involving JAK2 and β-catenin, which further inhibited PP2A.
- - Treatment with PP2A-activating drugs (PADs) significantly impaired the survival and self-renewal of these CML
Article Synopsis
- Indole-3-carbinol (I3C), a compound found in Brassica vegetables, shows potential as a cancer prevention and therapy agent by targeting Cdc25A phosphatase.
- The study found that I3C causes the degradation of Cdc25A, leading to cell cycle arrest at the G(1) phase and inhibiting the growth of breast cancer cells.
- The research highlights that the ATM-Chk2 pathway is crucial for I3C's effects, and mutations in Cdc25A can affect its responsiveness to I3C, suggesting new ways to tackle cancers with high Cdc25A levels.
CpG island tumor suppressor promoter methylation in non-BRCA-associated early mammary carcinogenesis.
Cancer Epidemiol Biomarkers Prev
March 2009
Article Synopsis
- Only 5% of breast cancers are linked to BRCA1/2 mutations, while the role of tumor suppressor gene methylation in familial cases remains unclear.
- A study examined CpG island promoter methylation in 109 high-risk women, revealing that methylation frequency increased with age, but specific methylation events were not age-related.
- Women without BRCA1/2 mutations showed significantly higher levels of methylation compared to those with mutations, indicating a potential link between methylation of tumor suppressor genes and non-BRCA1/2 familial breast cancer.
Purpose: Currently, we lack biomarkers to predict whether high-risk women with mammary atypia will respond to tamoxifen chemoprevention.
Experimental Design: Thirty-four women with cytologic mammary atypia from the Duke University High-Risk clinic were offered tamoxifen chemoprevention. We tested whether ESR1 promoter hypermethylation and/or estrogen receptor (ER) protein expression by immunohistochemistry predicted persistent atypia in 18 women who were treated with tamoxifen for 12 months and in 16 untreated controls.
Article Synopsis
- The study investigates the role of p16(INK4a) in cell cycle regulation and its absence in human mammary epithelial cells, which may lead to increased risk of breast cancer through various dysfunctions and DNA methylation changes.
- Researchers tested for hypermethylation of the INK4a/ARF promoter in breast tissue samples from 86 asymptomatic women at high risk for breast cancer, alongside evaluating correlation with other methylation markers.
- Results showed that INK4a/ARF promoter hypermethylation occurs in early stages of neoplasia and normal cells, indicating a potential indicator of broader methylation issues in breast cancer risk, rather than being solely an age-related change.
Hypermethylation of the breast cancer-associated gene 1 promoter does not predict cytologic atypia or correlate with surrogate end points of breast cancer risk.
Gregory R Bean Catherine Ibarra Drendall Vanessa K Goldenberg Joseph C Baker Michelle M Troch Carolyn Paisie
Cancer Epidemiol Biomarkers Prev
January 2007
Article Synopsis
- BRCA1 mutations are linked to familial breast cancer, but the impact of BRCA1 promoter hypermethylation in sporadic cases is unclear.
- A study assessed the frequency of BRCA1 promoter hypermethylation in 14 breast cancer biopsies and 61 high-risk women’s cytologic samples, finding similar rates across groups regardless of cytologic atypia.
- Results indicated that BRCA1 promoter hypermethylation is not tied to family history of breast cancer or traditional risk assessment models but is associated with age and the hypermethylation of certain other genes.