Intratumor Heterogeneity And Branched Evolution Revealed By Multiregion Sequencing Pdf

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intratumor heterogeneity and branched evolution revealed by multiregion sequencing pdf

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Intratumor heterogeneity may foster tumor evolution and adaptation and hinder personalized-medicine strategies that depend on results from single tumor-biopsy samples. To examine intratumor heterogeneity, we performed exome sequencing, chromosome aberration analysis, and ploidy profiling on multiple spatially separated samples obtained from primary renal carcinomas and associated metastatic sites.

Intratumor heterogeneity and branched evolution revealed by multiregion sequencing.

Tumor Heterogeneity View all 7 Articles. Today, clinical evaluation of tumor heterogeneity is an emergent issue to improve clinical oncology. In particular, intra-tumor heterogeneity ITH is closely related to cancer progression, resistance to therapy, and recurrences. It is interconnected with complex molecular mechanisms including spatial and temporal phenomena, which are often peculiar for every single patient. It is important to consider the different types of ITH as a whole for any patient to investigate on cancer progression, prognosis, and treatment opportunities.

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Adrenocortical carcinoma is a rare cancer with poor but heterogeneous prognosis. The main prognostic factors used in clinical practice at present are the tumor extension, best reflected by the ENSAT stage 2 , and the tumor proliferation, estimated either by mitotic count 3 or Ki67 proliferation index 4 , 5. However, the prognosis still varies widely among tumors with the same tumor stage and proliferation index 6. Recently, pan-genomic studies have identified molecular subtypes closely associated with prognosis 7 , 8. This subgroup is associated with very poor outcome.

Overview on Clinical Relevance of Intra-Tumor Heterogeneity

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Either your web browser doesn't support Javascript or it is currently turned off. In the latter case, please turn on Javascript support in your web browser and reload this page. Free to read. Intratumor heterogeneity may foster tumor evolution and adaptation and hinder personalized-medicine strategies that depend on results from single tumor-biopsy samples. To examine intratumor heterogeneity, we performed exome sequencing, chromosome aberration analysis, and ploidy profiling on multiple spatially separated samples obtained from primary renal carcinomas and associated metastatic sites. We characterized the consequences of intratumor heterogeneity using immunohistochemical analysis, mutation functional analysis, and profiling of messenger RNA expression. Intratumor heterogeneity was observed for a mutation within an autoinhibitory domain of the mammalian target of rapamycin mTOR kinase, correlating with S6 and 4EBP phosphorylation in vivo and constitutive activation of mTOR kinase activity in vitro.

Recent advances in next-generation sequencing have opened a new prospect in the field of cancer genomics and cancer evolution. Using next-generation sequencing, researchers have revealed that the occurrence of somatic events such as mutations and copy number alterations is associated with tumor evolution and genomic diversity in tumors, which is known as tumor heterogeneity 1. Tumor heterogeneity includes interpatient tumor heterogeneity 2 , intratumoral heterogeneity 3 , 4 , intermetastatic heterogeneity 5 - 8 , and intrametastatic heterogeneity 9. Tumor heterogeneity is a key factor associated with heterogeneous treatment responses including cancer progression, relapse and drug resistance Primary lung cancers harbor a larger mutational burden compared to other cancers, which might be a reason of poor treatment outcomes in patients with primary lung cancer 1 , 11 -


Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing To examine intratumor heterogeneity, we performed exome sequencing, chromosome Supplementary appendix. Click here to view.(34M, pdf). Go to.


Intratumor heterogeneity of prognostic DNA-based molecular markers in adrenocortical carcinoma

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Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. An Author Correction to this article was published on 29 January

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Intratumor heterogeneity and branched evolution revealed by multiregion sequencing

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Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing By demonstrating extensive intratumour heterogeneity, the studies by.


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1 Comments

  1. Curtis D. 18.04.2021 at 11:22

    Intratumor Heterogeneity and Branched Evolution Revealed. by Multiregion Sequencing. Marco Gerlinger, M.D., Andrew J. Rowan.