Publications by authors named "Carolyn A 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
- - 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
- - 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.
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