Publications by authors named "Gregory A Thomas"
Article Synopsis
- Replication repair deficiency, resulting from mismatch repair deficiency (MMRD) and/or loss of DNA polymerase proofreading, leads to hypermutation in cancer, with microsatellite instability (MSI) being a key indicator of MMRD.
- Genome-wide analysis reveals a connection between loss of polymerase proofreading and MSI, particularly when both replication repair mechanisms are compromised, highlighting distinct mutation signatures (MS-sigs).
- The study emphasizes the clinical utility of MS-sigs in identifying replication repair deficiencies in cancer patients and predicting their responses to immunotherapy, enhancing diagnosis and treatment strategies.
Replication repair deficiency (RRD) leading to hypermutation is an important driving mechanism of high-grade glioma (HGG) occurring predominantly in the context of germline mutations in RRD-associated genes. Although HGG presents specific patterns of DNA methylation corresponding to oncogenic mutations, this has not been well studied in replication repair-deficient tumors. We analyzed 51 HGG arising in the background of gene mutations in RRD utilizing either 450 k or 850 k methylation arrays.
View Article and Find Full Text PDFWe present an extensive assessment of mutation burden through sequencing analysis of >81,000 tumors from pediatric and adult patients, including tumors with hypermutation caused by chemotherapy, carcinogens, or germline alterations. Hypermutation was detected in tumor types not previously associated with high mutation burden. Replication repair deficiency was a major contributing factor.
View Article and Find Full Text PDFWe present an unusual pediatric case of invasive upper tract urothelial carcinoma with an associated genetic predisposition. A 14-year-old female presented with intermittent right flank pain, and was found to have a poorly functioning hydronephrotic right kidney. Laparoscopic nephrectomy was performed.
View Article and Find Full Text PDFObjective: To evaluate both the cholinesterase monitoring program and newer field methods of determining coumaphos exposure among tick eradication workers.
Methods: Measured blood cholinesterase by the Ellman and field testing methods and tested urine for chlorferon pre- and postshift; conducted personal air sampling, patch sampling of clothing, and wipe sampling of hands for coumaphos.
Results: Fifteen workers had normal plasma cholinesterase and acetylcholinesterase levels.
Safer schools in an age of mass violence: back to the basics of public health.
Disaster Med Public Health Prep
September 2007
Background: Effective ways to prevent arthropathy in severe hemophilia are unknown.
Methods: We randomly assigned young boys with severe hemophilia A to regular infusions of recombinant factor VIII (prophylaxis) or to an enhanced episodic infusion schedule of at least three doses totaling a minimum of 80 IU of factor VIII per kilogram of body weight at the time of a joint hemorrhage. The primary outcome was the incidence of bone or cartilage damage as detected in index joints (ankles, knees, and elbows) by radiography or magnetic resonance imaging (MRI).
Background: Patients with Glanzmann thrombasthenia (GT) have normal platelet counts but abnormal platelet aggregation and carry the risk of life-threatening bleeding. We report three patients who received bone marrow transplantation (BMT) for type I GT and discuss the risk and management of anti-platelet antibodies.
Patients And Results: Diagnosis of GT was made through abnormal platelet aggregation studies or the absence of GPIIb/IIIa by flow cytometry.