Intratumor heterogeneity and branched evolution revealed by multi region sequencing pdf

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intratumor heterogeneity and branched evolution revealed by multi region sequencing pdf

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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.

Tumour evolution: from linear paths to branched trees

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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. This subgroup is associated with a better outcome.

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.

Intratumor heterogeneity and branched evolution revealed by multiregion sequencing.

The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors. Comprehensive genomic analyses of cancers have revealed substantial intrapatient molecular heterogeneities that may explain some instances of drug resistance and treatment failures. Examination of the clonal composition of an individual tumor and its evolution through disease progression and treatment may enable identification of precise therapeutic targets for drug design. Multi-region and single-cell sequencing are powerful tools that can be used to capture intratumor heterogeneity. We collected over tumor samples from patients corresponding to 45 different types of cancer.

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. The advent of next-generation sequencing technologies enabled the characterization of cancer genomes at unprecedented resolution Milestone 7. Insights into the genomic landscapes of some cancers promised to move cancer treatment towards genotype-guided approaches.

Skip to search form Skip to main content You are currently offline. Some features of the site may not work correctly. DOI: Gerlinger and Andrew J. Rowan and S. Horswell and M. Math and J.


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


Overview on Clinical Relevance of Intra-Tumor Heterogeneity

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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.

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

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