Publications by authors named "Carol Beadling"
Article Synopsis
- Diffuse gliomas are complex brain tumors that often cannot be completely removed through surgery, leading to treatment with chemotherapy and radiation.* -
- Recurrent gliomas may have genetic alterations that affect their behavior and resistance to previous treatments, particularly when treated with the chemotherapy drug temozolomide.* -
- A study of eleven pediatric patients showed that increased tumor mutation burden at recurrence is significant, especially in cases of H3 G34-mutant diffuse hemispheric gliomas.*
Mechanisms of targeted therapy resistance in a pediatric glioma driven by fusion.
Cold Spring Harb Mol Case Stud
October 2021
Article Synopsis
- Some cancer genes can mix together in a way that leads to new cancer types, and doctors try to target these with special treatments.
- Even though some treatments worked initially, some kids’ brain tumors developed ways to resist these treatments, making it hard for doctors to help.
- Researchers studied these tough tumors and found new genes that were causing the resistance, showing how they can help improve future treatments to fight these cancers better.
GAB1-ABL1 fusions in tumors that have histologic overlap with NTRK-rearranged spindle cell tumors.
Genes Chromosomes Cancer
September 2021
Article Synopsis
- Fibroblastic spindle cell tumors are rare soft tissue tumors linked to genetic mutations, specifically kinase gene fusions, with a focus on GAB1-ABL1 fusions in two reported cases.
- The first case involves a 76-year-old woman with a significant tumor showing distinct cell patterns and successful treatment response to the drug imatinib.
- The second case is a 9-year-old girl originally diagnosed with a solitary fibrous tumor, which also showed a GAB1-ABL1 fusion upon further genetic analysis, highlighting the complexity and treatment potential of these tumors through advanced sequencing techniques.
Article Synopsis
- Recent studies show that while most infantile fibrosarcomas (IFS) have the ETV6-NTRK3 translocation, there are tumors with similar characteristics caused by various other genetic fusions, including BRAF.
- This report details 14 BRAF-altered tumors, revealing a mix of BRAF fusions and mutations, with significant variations in their molecular profiles.
- The findings enhance our understanding of these tumors' characteristics, suggesting new targets for treatment and helping improve diagnostic methods for similar mesenchymal tumors.
Article Synopsis
- * A new precision oncology platform integrates serial biopsies, multi-omic analyses, and patient monitoring to gain a better understanding of each patient's unique cancer ecosystem.
- * The study reveals significant differences in receptor status and genomic alterations among lesions, suggesting that repeat biopsies could help refine targeted therapies for patients with rapidly progressing or mixed responses to treatment.
Article Synopsis
- Activating mutations in receptor tyrosine kinase are early indicators of gastrointestinal stromal tumors (GISTs), but these mutations alone don’t lead to malignancy, as seen in many individuals with micro-GISTs.
- Whole exome sequencing of GISTs from 21 patients revealed significant alterations in cell cycle genes, with low mutations suggesting limited effectiveness of immunotherapy.
- In an independent study, mutations in cell cycle-related genes correlated with higher risk categories and were linked to significantly shorter relapse-free and overall survival rates.
Article Synopsis
- * A significant number of genetic alterations in these SDH genes are classified as variants of unknown significance (VUS), which complicates risk assessment for patients.
- * This study employs clinical data, a yeast model, and computational analysis to evaluate 22 VUS, concluding that 73% are pathogenic and affect SDH function, emphasizing the need for better assessments of these genetic variants.
Article Synopsis
- KIT, PDGFRA, NF1, and SDH mutations are early triggers for hyperplasia in gastrointestinal stromal tumors (GISTs), but more changes are needed for them to become cancerous.
- Chromosome 14q deletion is the most common secondary change found in about 70% of GISTs, and 21% of GIST cases in a study showed mutations in the MAX gene on this chromosome.
- MAX mutations are particularly prevalent in GISTs related to NF1 syndrome and lead to a loss of p16 protein expression, which plays a role in regulating the cell cycle, therefore contributing to the progression of GISTs.
Article Synopsis
- * A next-generation sequencing method using a multiplex PCR-based panel effectively identifies fusion transcripts from 19 driver genes and 94 partner genes associated with solid tumors, including control assays for detecting unidentified fusions.
- * The new panel showed strong agreement with traditional methods in correctly identifying fusion genes in cancer specimens and provided insights through 3'/5' expression ratios; however, further validation was needed for some predicted fusions.
Article Synopsis
- - Understanding BRAF V600E mutations is crucial for determining the right treatment for patients, especially those with gastrointestinal stromal tumors (GISTs), as these mutations are responsive to BRAF inhibitors.
- - In a study of 38 GIST patients, immunohistochemistry and BRAF sequencing were used to assess mutation presence, revealing that only 5% had strong BRAF expression, while 21% had weak expression, and 74% showed no expression.
- - The findings suggest that BRAF V600E mutation-specific immunohistochemistry is an effective and reliable technique for identifying BRAF-mutated GISTs, which could help guide therapy decisions.
Novel mutations in neuroendocrine carcinoma of the breast: possible therapeutic targets.
Appl Immunohistochem Mol Morphol
February 2015
Article Synopsis
- Primary neuroendocrine carcinoma of the breast is a rare and aggressive form of breast cancer, comprising only 2% to 5% of cases.
- A study identified genetic mutations in neuroendocrine breast tumors, revealing that PIK3CA mutations are prevalent, while mutations in FGFR and RAS family members are rare.
- This research highlights the importance of comprehensive genetic analysis in understanding and potentially treating uncommon tumors like neuroendocrine breast carcinoma.
Article Synopsis
- A basket clinical trial was conducted to evaluate the effectiveness of various targeted therapies on different cancer types with specific genetic mutations, focusing on patients with advanced lung cancer and thymic malignancies.
- Six hundred forty-seven patients were enrolled, with genomic testing revealing significant mutation frequencies for EGFR (22.1%) and KRAS (24.9%), leading to variable response rates to treatments like erlotinib and selumetinib.
- Although the trial design faced challenges with feasibility for arms targeting rare mutations, it provided valuable insights into the genetic profiles and survival outcomes of the studied malignancies.
Article Synopsis
- Changes in gene copy number are crucial for precision medicine, and this study focuses on assessing copy number alterations (CNAs) in amplicon-based sequencing methods, which have been less explored compared to hybridization-capture libraries.
- The researchers developed a detection algorithm that showed high concordance with CNAs found in hybridization-capture libraries and found that pooled normal sequence data could replace matched normal tissue without diminishing detection accuracy for significant CNAs.
- The study also confirmed that the algorithm performed well compared to traditional methods like array comparative genomic hybridization and fluorescence in situ hybridization, with successful detection influenced by factors such as the number of gene amplicons, average read depth, and tumor content in the samples.
Article Synopsis
- Resistant KIT mutations complicate the effectiveness of KIT kinase inhibitors in treating systemic mastocytosis, prompting research into a combination therapy.
- The study tested a novel approach that combines a KIT inhibitor with a calcineurin phosphatase inhibitor (CNPI) on KIT-mutant mast cell lines, revealing that this combination reduced cell survival and triggered apoptosis.
- Findings indicate that NFAT is consistently active in these mutant cells, and targeting both KIT and NFAT could offer a potential new treatment strategy for mast cell diseases.
Article Synopsis
- The study investigates the genetic mutations associated with melanomas and melanocytic nevi in the female genital tract, focusing on specific genes: BRAF, NRAS, KIT, GNA11, and GNAQ.
- Researchers screened 25 melanoma samples, 7 benign melanocytic nevi, and 4 atypical melanocytic nevi to identify mutation frequencies.
- Findings revealed that KIT, NRAS, and BRAF mutations occur in some female genital tract melanomas, while BRAF mutations were common in benign nevi, highlighting the need for further genetic screening for effective treatments.
Article Synopsis
- Gallbladder cancer is a serious disease that's often found late, and its genetic makeup is not well understood, prompting this study to identify mutations that could aid in early diagnosis and treatment.
- The researchers analyzed 49 gallbladder cancer cases using specialized technology to check for mutations in 30 genes, finding notable mutations in four specific genes in a small number of cases.
- The results align with existing literature and suggest that discovering mutations like PIK3CA and KRAS could lead to better-targeted therapies, highlighting the need for more extensive research to uncover additional genetic targets.
Article Synopsis
- The study aimed to identify actionable mutations in patients with high-risk localized prostate cancer to aid in developing targeted therapies.
- Researchers analyzed tumor samples for common mutations and specific protein markers using sequencing and immunohistochemistry.
- Results revealed that while point mutations in cancer genes were rare (10%), PTEN loss was associated with shorter relapse-free survival, highlighting its potential importance in treatment outcomes.
Article Synopsis
- * In a study of 22 radial scars, 63.6% were found to have activating mutations in the PIK3CA gene, which is commonly seen in invasive breast cancers, with a notably higher mutation rate compared to typical invasive cases.
- * The presence of PIK3CA mutations in radial scars raises new questions about their role in the development of breast cancer, indicating a need for larger studies to explore the relationship between these lesions and cancer risk further.
Article Synopsis
- The phosphatidylinositol-3-kinase (PIK3CA) pathway is commonly mutated in invasive breast cancer, with about 25% of cases showing PIK3CA mutations.
- A study screened 192 breast lesions for genetic mutations, finding that PIK3CA mutations were present in various types of breast tissue, including proliferative lesions and atypical hyperplasia.
- The research indicates significant genetic differences between benign proliferative lesions and concurrent invasive cancer, suggesting that while proliferative lesions may carry mutations, they do not necessarily lead to cancer, highlighting their complex role in breast cancer development.
Article Synopsis
- - Gastrointestinal stromal tumors (GISTs) are tumors in the GI tract originating from interstitial cells of Cajal, with the majority having mutations in KIT or PDGFRA, while about 10-15% of adult and 85% of pediatric GISTs are mutation-free.
- - "Wild-type" GISTs often show high levels of the insulin-like growth factor 1 receptor (IGF1R), leading to trials for targeted IGF1R therapy, although not all might express IGF1R.
- - The study analyzed 136 GISTs and identified various wild-type subpopulations based on IGF1R expression and other factors, highlighting the diversity of wild-type GIST