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The first human genome sequencing project cost $2.7 billion and was declared complete in 2003, after 15 years of international cooperation and collaboration between several research teams and funding agencies. Today, with the advent of next-generation sequencing technologies, the cost and time of sequencing a human genome have dropped over 100 fold.
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The Mitotic Spindle02:27

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The mitotic spindle—or spindle apparatus—is a eukaryotic, cytoskeletal structure made up of long protein fibers called microtubules. Formed during cell division, the spindle separates sister chromatids and moves them to opposite ends of a parental cell, where the now individual chromosomes are distributed to two daughter cell nuclei.
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The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
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Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
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Sequences are fundamental mathematical objects consisting of ordered lists of numbers that follow a specific rule or pattern. Sequences are critical in various mathematical concepts, including calculus, series, and number theory. They can model real-world phenomena such as population growth, financial investments, and physical processes like the diminishing height of a bouncing ball.Each number in a sequence is referred to as a term. Typically, the terms are denoted as a1, a2, a3,…, where...
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Isolation of Myeloid Dendritic Cells and Epithelial Cells from Human Thymus
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Spindle Epithelial Tumor with Thymus-Like Differentiation (SETTLE): A Next-Generation Sequencing Study.

Todd M Stevens1, Diana Morlote2, Jeff Swensen3

  • 1Department of Pathology, University of Alabama at Birmingham, 3548 North Pavilion, 1802 6th Ave South, Birmingham, AL, 35249, USA. tstevens@uabmc.edu.

Head and Neck Pathology
|May 9, 2018
PubMed
Summary

This study investigated the genetic landscape of Spindle Epithelial Tumor with Thymus-like differentiation (SETTLE), a rare neck neoplasm. Researchers identified novel KMT2D, KMT2C, and NRAS gene variants in SETTLE cases, offering new insights into its molecular basis.

Keywords:
Molecular diagnosticsNext-generation sequencingSETTLEThyroid

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Area of Science:

  • Oncology
  • Genetics
  • Pathology

Background:

  • Spindle epithelial tumor with thymus-like differentiation (SETTLE) is a rare, malignant biphasic neoplasm.
  • SETTLE primarily affects the thyroid or neck and can metastasize late.
  • SETTLE is morphologically similar to synovial sarcoma but lacks its characteristic translocations.

Purpose of the Study:

  • To conduct comprehensive next-generation sequencing on SETTLE cases.
  • To identify the molecular alterations driving SETTLE pathogenesis.
  • To differentiate SETTLE from its mimics through molecular profiling.

Main Methods:

  • Direct sequence analysis of 592 genes across 5 SETTLE cases.
  • Fusion gene analysis of 52 frequently rearranged cancer genes.
  • Next-generation sequencing (NGS) for comprehensive genomic profiling.

Main Results:

  • Identified pathogenic variants in KMT2D (splice site and frameshift) and KMT2C (nonsense) in one SETTLE case.
  • Detected a pathogenic NRAS missense variant (Q61R) in a second SETTLE case.
  • Found no other molecular alterations, including microsatellite instability, gene fusions, or amplifications.

Conclusions:

  • This study provides the first comprehensive molecular analysis of SETTLE.
  • Identified specific genetic variants (KMT2D, KMT2C, NRAS) in SETTLE, contributing to understanding its tumorigenesis.
  • The findings help distinguish SETTLE from other neoplasms and may guide future therapeutic strategies.