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Genetic lesion associated with cancer

a gene and cancer technology, applied in the field of cancer and molecular biology, can solve the problems of increased risk of developing cancer, increased occurrence of secondary, and increased risk of lcs6 snp, and achieve the effect of increasing the risk of cancer

Inactive Publication Date: 2010-07-29
YALE UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The LCS6 SNP significantly increases the risk of developing aggressive forms of cancer, enabling early identification and potential prevention of cancers through minimally invasive surgeries and targeted therapies, improving prognosis and reducing mortality rates.

Problems solved by technology

Subjects carrying a particular SNP, referred to herein as the LCS6 SNP, have a significantly increased risk of developing cancer.
Moreover, the occurrence of the LCS6 SNP is associated with earlier onset of cancer, increased occurrence of secondary cancers (including multiple secondary cancers), and increased occurrence of particularly aggressive or high risk forms of cancer.

Method used

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  • Genetic lesion associated with cancer
  • Genetic lesion associated with cancer
  • Genetic lesion associated with cancer

Examples

Experimental program
Comparison scheme
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example 1

General Methods

Study Populations

[0209]Lung tissue samples from patients with a diagnosis of NSCLC were collected following Yale University Human Investigation Committee approval. Cases were chosen based on the availability of frozen stored tissue from lung tumor resections from 1994 through 2003, and from recent cases with extra tissue available. Tissue was collected from 87 patients. Seven patients were excluded due to other risk factors for lung cancer (e.g., immunosuppression, tuberculosis) and six were excluded due to their tumors being non-lung primary metastatic disease. Seventy-four patients were included in the analysis (Table 2).

TABLE 2Yale NSCLC patient characteristics.Pa-Pack-LCS6-tientSexPopulationAgeYearCancer TypeSNP1FCaucasian64150AdenocarcinomaN2MCaucasian7320AdenosquamousN3MCaucasian6450Large cellN4FCaucasian76unknownAdenocarcinomaN5MHispanic5470Squamous cellN6MCaucasian6410Squamous cellY7MCaucasian8660Squamous cellN8FCaucasian540AdenocarcinomaN9FCaucasian5840Adenos...

example 2

Identification of a Candidate let-7 SNP

[0220]let-7 complementary sites (LCSs) were sequenced in the KRAS 3′ untranslated region (UTR) from 74 non-small cell lung cancer (NSCLC) cases to identify mutations and single nucleotide polymorphisms (SNPs) that correlated with NSCLC. A candidate SNP was identified and the allele frequency was determined by typing the polymorphism in 2433 people (representing 46 human populations). The association was further assessed between the SNP and the risk of smoking-induced NSCLC in two independent case-control studies.

[0221]The novel SNP was identified in an LCS in 24% of Caucasian NSCLC patients, compared to 7.4% of the general Caucasian population. The presence of the SNP predicted for squamous cell carcinoma versus adenocarcinoma and a positive family history of cancer. The variant allele at the SNP is associated with earlier onset NSCLC (50 years of age) and additional cancer diagnoses. The frequency of the variant is 20.3% in our cohort of NSCLC...

example 3

Identification of a SNP in a let-7 Complementary Site in the KRAS 3′UTR

[0223]RAS expression is regulated in a 3′UTR and let-7-dependent manner through ten putative let-7 complementary sites (LCSs) in the human KRAS 3′UTR (FIG. 23A) (Johnson, S. M. et al. Cell 2005; 120(5): 635-47). Based on data from the HapMap (Consortium TIH. Nature 2003; 426:789-96) and dbSNP (Sherry, S. et al. Genome Res 1999; 9:677-9) databases, only one SNP, rs712(−), is reported in an LCS. Tissue from seventy-four patients with NSCLC exhibited changes from the reference human sequence in at least one LCSs. Changes in LCS1, LCS9, and LCS4 (Table 7) did not appear to correlate with NSCLC. However, a SNP (T to G, with G the less frequent variant) identified at the fourth nucleotide in LCS6 was found in 20.3% of the NSCLC patients (FIG. 20B-20D). Supporting the hypothesis that the variant allele at this SNP is a genetic marker of increased lung cancer risk, an increased frequency of the allele was found in younge...

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Abstract

The invention comprises methods for identifying mutations within the 3′ UTRs of genes that lead to increased risk or probability of developing cancer.

Description

RELATED APPLICATIONS[0001]This application is related to provisional applications U.S. Ser. No. 60 / 932,575, filed May 31, 2007, U.S. Ser. No. 61 / 001,965, filed Nov. 5, 2007, U.S. Ser. No. 61 / 065,745 filed Feb. 14, 2008, and U.S. Ser. No. 61 / 124,610, filed Apr. 18, 2008, the contents which are each herein incorporated by reference in their entirety.FIELD OF THE INVENTION[0002]This invention relates generally to the fields of cancer and molecular biology. The invention provides compositions and methods for predicting increased risk of developing cell proliferative diseases, such as cancer.BACKGROUND OF THE INVENTION[0003]Even though there has been progress in the field of cancer detection, there still remains a need in the art for the identification of new genetic markers for a variety of cancers that can be easily used in clinical applications. To date, there are relatively few options available for predicting the risk of developing cancer.[0004]A test for predicting the risk of deve...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C07H21/00
CPCC12Q1/6886C12Q2600/118C12Q1/6827C12Q2600/178C12Q2600/172C12Q2600/156
Inventor SLACK, FRANK J.WEIDHAAS, JOANNE B.CHIN, LENA J.RATNER, ELENA
Owner YALE UNIV