Objective: RAS mutations are the most common mutations in thyroid nodules with indeterminate cytology by fine-needle aspiration cytology (FNAC), and are mutually exclusive with BRAF mutations. However, the diagnostic utility of RAS mutation analysis is uncertain. We evaluated the diagnostic utility of RAS mutation analysis in indeterminate thyroid nodules.
Design, Patients, And Measurements: A total of 155 thyroid nodules (90 benign and 65 indeterminate) negative for BRAF(V) (600E) mutations on FNAC were analysed for mutations in RAS codon 61 using pyrosequencing methods. We evaluated diagnostic accuracy of RAS mutation for predicting thyroid malignancy based on the surgical pathologic diagnosis.
Results: Among the 65 BRAF(V) (600E) -negative indeterminate thyroid nodules identified by FNAC, 25 (38·5%) exhibited point mutations in RAS 61 consisting of 18 NRAS 61 (72%), and 7 HRAS 61 (28%) mutations. In contrast, only five of 90 (5·6%) nodules with benign cytology had RAS mutations. Only two of 25 (8·0%) RAS 61(+) indeterminate nodules exhibited malignant ultrasonographic features. Of the 15 patients with RAS 61(+) -indeterminate nodules who underwent thyroid surgery, 14 (93·3%) were diagnosed as malignant, including 13 follicular variant of papillary thyroid carcinomas (FVPTC), and one follicular thyroid carcinoma (FTC). The average tumour size was 1·79 ± 0·62 cm. Multifocality was seen in 28·6% of cases, with 7·1% exhibiting extrathyroidal extension; no lymph node or distant metastases were evident. Based on the surgical pathologic diagnosis results, preoperative RAS 61 mutation analysis on FNAC exhibited 93·3% sensitivity, 75·0% specificity, 93·3% positive predictive value, 75·0% negative predictive value and 89·5% diagnostic accuracy for predicting malignancies.
Conclusion: Our results suggest that RAS mutation analysis holds great promise as a preoperative diagnostic tool for predicting FVPTC in cytologically and sonographically indeterminate nodules negative for BRAF mutations.
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http://dx.doi.org/10.1111/cen.12579 | DOI Listing |
Discov Oncol
December 2024
Dr B R Ambedkar Center for Biomedical Research, University of Delhi, Delhi, 110007, India.
Cancer, a leading cause of death worldwide, is projected to increase by 76.6% in new cases and 89.7% in mortality by 2050 (WHO 2022).
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December 2024
Center for Multiple Myeloma, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Multiple myeloma (MM) remains incurable despite novel therapeutics. A major contributor to the development of relapsed/refractory and resistant MM is extraosseous extramedullary disease (EMD), whose molecular biology is still not fully understood. We analyzed 528 MM patients who presented to our institution between 2014 and 2021 and who had undergone molecular testing.
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December 2024
Department of Pharmaceutical Sciences, School of Health Sciences and Technology, UPES Dehradun - 248007, Uttarakhand, India. Electronic address:
KRAS (Kirsten rat sarcoma viral oncogene homologue), the most common mutated protein in human cancers, is the leading cause of morbidity and mortality. Before Sotorasib (AMG-510) was approved for non-small cell lung cancer treatment in 2020, the oncogenic KRAS mutations were believed to be non-druggable. High-resolution X-ray crystal structures of GDP-bound KRAS mutants with and without inhibitor resolved.
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AMES, Centro Polidiagnostico Strumentale srl, Via Padre Carmine Fico 24, Casalnuovo Di Napoli 80013, Italy.
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J Mol Biol
December 2024
Division of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA; University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. Electronic address:
Rho family GTPases are a part of the Ras superfamily and are signaling hubs for many cellular processes. While the detailed understanding of Ras structure and function has led to tremendous progress in oncogenic Ras-targeted drug discovery, studies of the related Rho GTPases are also catching up as the recurrent cancer-related Rho GTPase mutations have only been discovered in the last decade. Like that of Ras, an in-depth understanding of the structural basis of how Rho GTPases and their mutants behave as key oncogenic drivers benefits the development of clinically effective therapies.
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