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Genome-wide analyses of structural a...

Leary, Rebecca J.

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Genome-wide analyses of structural alterations in human cancer.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Genome-wide analyses of structural alterations in human cancer./
Author:	Leary, Rebecca J.
Description:	142 p.
Notes:	Source: Dissertation Abstracts International, Volume: 71-05, Section: B, page: 2804.
Contained By:	Dissertation Abstracts International71-05B.
Subject:	Biology, Genetics. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3407676
ISBN:	9781109775891

Genome-wide analyses of structural alterations in human cancer.
Leary, Rebecca J.

Genome-wide analyses of structural alterations in human cancer. - 142 p.

Source: Dissertation Abstracts International, Volume: 71-05, Section: B, page: 2804.

Thesis (Ph.D.)--The Johns Hopkins University, 2010.

A comprehensive understanding of the genetic alterations underlying human cancers comprises both sequence and structural alterations. We have developed novel approaches for detection of structural alterations using high density SNP arrays and massively parallel next generation sequencing. We then applied these techniques, together with the tag-based Digital Karyotyping approach, to the analysis of copy number alterations in human colorectal, breast, brain and pancreatic tumors. These studies identified a large number of focal, high-copy amplifications and homozygous deletions, which were combined with sequence alteration data to identify genes and cellular pathways affected by both copy number changes and point alterations. These analyses provided an integrated view of copy number and sequencing alterations on a genome-wide scale, yielding a comprehensive view of genetic alterations in these tumor types and furthering our appreciation of the complexity of the cancer genome landscape. Integrated analyses of copy number and sequence alterations also identified genes and pathways that could prove useful for cancer diagnosis and therapy. In order to translate these analyses for clinical purposes, we created a method, called Personalized Analysis of Rearranged Ends (PARE) which can identify rearrangements in solid tumors that can be developed into patient-specific biomarkers. Analysis of over 1.1 billion sequences from breast and colorectal tumors revealed that each tumor contained multiple rearranged sequences that were suitable for use as biomarkers. Using PCR specific to the rearranged sequences, we were able to detect mutant DNA molecules present at levels lower than 0.001% and readily identified mutated circulating DNA in patient plasma samples. This approach provides an exquisitely sensitive and broadly applicable approach for the development of personalized biomarkers for the clinical management of cancer patients.

ISBN: 9781109775891Subjects--Topical Terms:

1017730
Biology, Genetics.

Genome-wide analyses of structural alterations in human cancer.
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245 1 0 $a Genome-wide analyses of structural alterations in human cancer.
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500 $a Source: Dissertation Abstracts International, Volume: 71-05, Section: B, page: 2804.
500 $a Advisers: Victor Velculescu; Bert Vogelstein.
502 $a Thesis (Ph.D.)--The Johns Hopkins University, 2010.
520 $a A comprehensive understanding of the genetic alterations underlying human cancers comprises both sequence and structural alterations. We have developed novel approaches for detection of structural alterations using high density SNP arrays and massively parallel next generation sequencing. We then applied these techniques, together with the tag-based Digital Karyotyping approach, to the analysis of copy number alterations in human colorectal, breast, brain and pancreatic tumors. These studies identified a large number of focal, high-copy amplifications and homozygous deletions, which were combined with sequence alteration data to identify genes and cellular pathways affected by both copy number changes and point alterations. These analyses provided an integrated view of copy number and sequencing alterations on a genome-wide scale, yielding a comprehensive view of genetic alterations in these tumor types and furthering our appreciation of the complexity of the cancer genome landscape. Integrated analyses of copy number and sequence alterations also identified genes and pathways that could prove useful for cancer diagnosis and therapy. In order to translate these analyses for clinical purposes, we created a method, called Personalized Analysis of Rearranged Ends (PARE) which can identify rearrangements in solid tumors that can be developed into patient-specific biomarkers. Analysis of over 1.1 billion sequences from breast and colorectal tumors revealed that each tumor contained multiple rearranged sequences that were suitable for use as biomarkers. Using PCR specific to the rearranged sequences, we were able to detect mutant DNA molecules present at levels lower than 0.001% and readily identified mutated circulating DNA in patient plasma samples. This approach provides an exquisitely sensitive and broadly applicable approach for the development of personalized biomarkers for the clinical management of cancer patients.
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790 1 0 $a Vogelstein, Bert, $e advisor
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