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Related Concept Videos

Mutations01:39

Mutations

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Overview
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Mutations01:35

Mutations

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Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
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Viral Mutations00:36

Viral Mutations

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A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
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Mutation, Gene Flow, and Genetic Drift01:09

Mutation, Gene Flow, and Genetic Drift

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In a population that is not at Hardy-Weinberg equilibrium, the frequency of alleles changes over time. Therefore, any deviations from the five conditions of Hardy-Weinberg equilibrium can alter the genetic variation of a given population. Conditions that change the genetic variability of a population include mutations, natural selection, non-random mating, gene flow, and genetic drift (small population size).
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Cancers Originate from Somatic Mutations in a Single Cell02:21

Cancers Originate from Somatic Mutations in a Single Cell

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Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
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Mutations in Microorganisms01:18

Mutations in Microorganisms

726
Mutations are heritable changes in an organism’s genome involving alterations in the base sequence of DNA or RNA. These changes can influence cellular processes and phenotypic traits, potentially transforming the unaltered wild type into a mutant form. Such changes, termed forward mutations, are pivotal in shaping the genetic diversity of organisms.RNA viruses exhibit the highest mutation rates due to the absence of robust proofreading mechanisms during genome replication. In contrast,...
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Related Experiment Video

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Modeling Spontaneous Metastatic Renal Cell Carcinoma mRCC in Mice Following Nephrectomy
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Mutations in renal cell carcinoma.

Christopher D'Avella1, Phillip Abbosh2, Sumanta K Pal3

  • 1Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA.

Urologic Oncology
|November 28, 2018
PubMed
Summary

Understanding the molecular basis of renal cell carcinoma (RCC) has improved treatments. Genetic mutations in clear cell RCC and papillary RCC are guiding new targeted therapies and immunotherapies for better patient outcomes.

Keywords:
Genetic mutationsMolecular geneticsMolecular profilingRenal cell carcinomaTargeted therapy

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A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
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Area of Science:

  • Urology
  • Oncology
  • Molecular Biology

Background:

  • Renal cell carcinoma (RCC) is a common urologic cancer with diverse subtypes.
  • Clear cell RCC (ccRCC) is the most frequent subtype, with sarcomatoid differentiation indicating a poor prognosis.
  • Historically, RCC treatment options were limited and toxic, with low response rates.

Purpose of the Study:

  • To review the molecular underpinnings of RCC subtypes.
  • To highlight advancements in targeted therapy and immunotherapy for RCC.
  • To discuss the prognostic implications of specific genetic mutations in RCC.

Main Methods:

  • Review of recent genomic sequencing studies in RCC.
  • Analysis of molecular alterations in clear cell, papillary, and sarcomatoid RCC.
  • Correlation of genetic mutations with treatment response and prognosis.

Main Results:

  • Von Hippel Lindau gene inactivation is common in ccRCC, leading to VEGF and mTOR inhibitors.
  • Key mutations in ccRCC include BAP-1, PBRM1, SETD2, and PIK3CA.
  • Papillary RCC shows frequent MET gene mutations, suggesting MET-targeted therapy utility.
  • TP53 and NF2 mutations are implicated in sarcomatoid tumor development.

Conclusions:

  • Advances in understanding RCC molecular genetics have diversified treatment options.
  • Targeted therapies and immunotherapies are improving outcomes for RCC patients.
  • Continued research into RCC's molecular drivers will further refine treatment strategies.