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Related Concept Videos

X-Inactivation01:58

X-Inactivation

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The human X chromosome contains over ten times the number of genes as in the Y chromosome. Since males have only one X chromosome, and females have two, one might expect females to produce twice as many of the proteins, with undesirable results.
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Metallic solids such as crystals of copper, aluminum, and iron are formed by metal atoms. The structure of metallic crystals is often described as a uniform distribution of atomic nuclei within a “sea” of delocalized electrons. The atoms within such a metallic solid are held together by a unique force known as metallic bonding that gives rise to many useful and varied bulk properties.
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Solids in which the atoms, ions, or molecules are arranged in a definite repeating pattern are known as crystalline solids. Metals and ionic compounds typically form ordered, crystalline solids. A crystalline solid has a precise melting temperature because each atom or molecule of the same type is held in place with the same forces or energy. Amorphous solids or non-crystalline solids (or, sometimes, glasses) which lack an ordered internal structure and are randomly arranged. Substances that...
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Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
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Network covalent solids contain a three-dimensional network of covalently bonded atoms as found in the crystal structures of nonmetals like diamond, graphite, silicon, and some covalent compounds, such as silicon dioxide (sand) and silicon carbide (carborundum, the abrasive on sandpaper). Many minerals have networks of covalent bonds.
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Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
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CDK12 inactivation across solid tumors: an actionable genetic subtype.

Catherine H Marshall1, Eddie L Imada2, Zhuojun Tang3

  • 1Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

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|July 31, 2019
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Summary

The study found that inactivating CDK12 mutations are most common in bladder, prostate, and uterine cancers. These findings are crucial for understanding potential therapeutic strategies across various cancer types.

Keywords:
CDK12biomarkersgeneticsimmunotherapyprostate cancer

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Area of Science:

  • Oncology
  • Genetics
  • Genomic Medicine

Background:

  • Inactivating alterations in Cyclin-Dependent Kinase 12 (CDK12) have been identified in ovarian and prostate cancers.
  • These mutations suggest potential therapeutic implications, but their prevalence across diverse cancer types remains largely unknown.

Purpose of the Study:

  • To determine the prevalence of monoallelic and biallelic CDK12 mutations across a wide range of cancer types.
  • To identify specific cancer types with a higher incidence of CDK12 alterations for further investigation.

Main Methods:

  • Utilized the cBioPortal and GENIE Project databases for comprehensive genomic data analysis.
  • Focused on cancer types with over 200 sequenced cases, including metastatic disease cohorts.
  • Applied a threshold of >1% occurrence for at least monoallelic CDK12 alterations to identify relevant cohorts.

Main Results:

  • The highest prevalence of monoallelic CDK12 mutations was observed in bladder cancer (3.7%), followed by prostate (3.4%), esophago-gastric (2.1%), and uterine cancers (2.1%).
  • Biallelic CDK12 inactivation was most frequent in prostate cancer (1.8%), followed by ovarian (1.0%) and bladder cancers (0.5%).
  • Analysis encompassed over 15,000 cases, providing a broad overview of CDK12 mutation frequencies.

Conclusions:

  • This study provides the first comprehensive estimation of CDK12 mutation prevalence across multiple cancer types.
  • The findings highlight bladder, prostate, and uterine cancers as key areas for further research into CDK12's role and therapeutic targeting.
  • Understanding CDK12 mutation prevalence is essential for developing targeted therapies and improving patient outcomes.