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Constitutively Decreased Transformin...

Pennison, Michael James.

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Constitutively Decreased Transforming Growth Factor Beta Receptor 1 (TGFBR1) Signaling Modifies Colorectal Cancer Predisposition.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Constitutively Decreased Transforming Growth Factor Beta Receptor 1 (TGFBR1) Signaling Modifies Colorectal Cancer Predisposition./
作者:	Pennison, Michael James.
面頁冊數:	162 p.
附註:	Source: Dissertation Abstracts International, Volume: 77-05(E), Section: B.
Contained By:	Dissertation Abstracts International77-05B(E).
標題:	Molecular biology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3741319
ISBN:	9781339335841

Constitutively Decreased Transforming Growth Factor Beta Receptor 1 (TGFBR1) Signaling Modifies Colorectal Cancer Predisposition.
Pennison, Michael James.

Constitutively Decreased Transforming Growth Factor Beta Receptor 1 (TGFBR1) Signaling Modifies Colorectal Cancer Predisposition. - 162 p.

Source: Dissertation Abstracts International, Volume: 77-05(E), Section: B.

Thesis (Ph.D.)--Northwestern University, 2015.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the third leading cause of cancer death in the United States. Twin cohort studies indicate that inherited susceptibility accounts for approximately 35% of all CRC cases, but only 5-6% of CRC cases can be attributed to known functional mutations. We were the first to identify a germline mutation in Transforming Growth Factor Beta Receptor 1 (TGFBR1) that is also somatically acquired in tumors, a 9 bp in frame deletion within exon 1 (rs11466445), which results in a receptor with decreased TGF-beta signaling properties. The observed association between this hypomorphic variant and cancer risk led us to hypothesize that constitutively decreased TGF-beta signaling may contribute to the development of CRC.

ISBN: 9781339335841Subjects--Topical Terms:

517296
Molecular biology.

Constitutively Decreased Transforming Growth Factor Beta Receptor 1 (TGFBR1) Signaling Modifies Colorectal Cancer Predisposition.
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245 1 0 $a Constitutively Decreased Transforming Growth Factor Beta Receptor 1 (TGFBR1) Signaling Modifies Colorectal Cancer Predisposition.
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500 $a Source: Dissertation Abstracts International, Volume: 77-05(E), Section: B.
500 $a Adviser: Boris C. Pasche.
502 $a Thesis (Ph.D.)--Northwestern University, 2015.
520 $a Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the third leading cause of cancer death in the United States. Twin cohort studies indicate that inherited susceptibility accounts for approximately 35% of all CRC cases, but only 5-6% of CRC cases can be attributed to known functional mutations. We were the first to identify a germline mutation in Transforming Growth Factor Beta Receptor 1 (TGFBR1) that is also somatically acquired in tumors, a 9 bp in frame deletion within exon 1 (rs11466445), which results in a receptor with decreased TGF-beta signaling properties. The observed association between this hypomorphic variant and cancer risk led us to hypothesize that constitutively decreased TGF-beta signaling may contribute to the development of CRC.
520 $a In this dissertation, we developed a novel mouse model of Tgfbr1 haploinsufficiency (Tgfbr1+/-) and found that Tgfbr1+/- mice were twice as likely as Tgfbr1+/+ mice to develop CRC. We subsequently identified two human haplotypes associated with constitutively decreased TGFBR1 expression and CRC risk and found that decreased TGFBR1 expression is strongly associated with three SNPs: rs7034462, rs11466445 and rs11568785. Further examination of TGFBR1 haplotype tagging SNPs suggests that the TGFBR1 rs7034462-TT is a novel moderate penetrance risk genotype, which has high penetrance among African Americans, the ethnic group with the highest risk for CRC. Our results provide strong support for the novel notion that rs7034462-TT is a potentially clinically relevant CRC susceptibility genotype that may identify individuals at high risk of dying from CRC.
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