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Methods and compositions for diagnosing and treating a colorectal adenocarcinoma

A technology for rectal adenocarcinoma and colon, which is applied in the field of diagnosis and treatment of colorectal adenocarcinoma and its composition, and can solve problems such as the lack of identification of gene markers

Inactive Publication Date: 2011-11-02
基督教高等教育科学研究及病人护理协会
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0007] However, no genetic markers (i.e., oncogenes) have been identified that are specifically linked to a given CRC-associated chromosomal aberration that would allow for the identification of adenocarcinomas and / or adenomas associated with specific types of chromosomal aberrations. adenocarcinoma progression

Method used

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  • Methods and compositions for diagnosing and treating a colorectal adenocarcinoma
  • Methods and compositions for diagnosing and treating a colorectal adenocarcinoma
  • Methods and compositions for diagnosing and treating a colorectal adenocarcinoma

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0189] Example 1 - Materials and methods

[0190] tumor sample

[0191] Forty-one formalin-fixed and paraffin-embedded colorectal adenomas (foci with adenocarcinoma, also called malignant polyps), and 73 prospectively collected snap-frozen colorectal tumor samples (37 nonprogressed adenomas and 36 adenocarcinomas) were studied. All samples were used in accordance with institutional ethics regulations.

[0192] The 41 progressive adenomas corresponded to 19 women and 18 men (three patients had more than one lesion). The mean age was 67 years (range 45-86). From these samples, the adenoma and carcinoma components were analyzed separately, increasing to a total of 82 archive samples (41x2).

[0193] The 73 frozen samples corresponded to 31 women and 34 men (6 patients with multiple tumors). The mean age was 69 years (range, 47-89). All histological sections were evaluated by a pathologist. Array CGH was performed on both sets of samples, while expression microarray ana...

Embodiment 2-20

[0221] The demarcation of the acquisition area on embodiment 2-20q

[0222] Forty-one progressive colorectal adenomas previously studied by classical CGH were analyzed with array CGH. The adenoma and adenocarcinoma components in these samples were tested separately. 20q gain occurs in more than 60% of cases ( Figure 1A , 1B; attached Figure 1A ). Although lower amplitudes are sometimes shown in the adenoma component ( Figure 1A and1B ), but the pattern of copy number changes did not differ between the adenoma and adenocarcinoma fractions (measured by CGHMultiArray).

[0223] Next, the DNA copy number status of 37 nonprogressive adenomas and 36 adenocarcinomas was analyzed. Of these 73 tumors, 67 (34 adenomas and 33 adenocarcinomas) showed high-quality genomic profiles with MAD values ​​ Figure 1C , 1D, attached Figure 1B ).

[0224] To identify the most relevant regions within 20q containing putative oncogenes that play a role in colorectal adenoma to adenocarcino...

Embodiment 3

[0225] Example 3 - Identification of Differentially Expressed Genes

[0226] Microarray expression analysis was performed on 37 non-progressive adenomas and 36 adenocarcinomas for which snap-frozen material was available. High-quality expression array data were obtained from 68 cases (37 adenomas and 31 adenocarcinomas, 7% flow rate).

[0227] Supervised data analysis to identify putative oncogenes on 20q was performed by two different approaches, we compared carcinomas to adenomas, and we compared tumors with 20q gain to tumors without 20q gain. The first method showed that there were 122 genes up-regulated genome-wide in carcinomas and 219 downregulated genes (341 differentially expressed genes in total). Among these 122 upregulated genes, 14 were mapped to chromosome 20q (Table 1). For the second approach, only tumors (adenoma and adenocarcinoma) with both array CGH data and expression data (n = 64) were included. As a pre-selection, genes differentially expressed (up...

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Abstract

The present invention relates to in vitromethods and compositions for diagnosing and / or treating a colorectal adenocarcinoma associated with a chromosomal aberration on chromosome 20q and / or the predisposition for developing such an adenocarcinoma by determining the expression levels of a set of particular marker genes, wherein an elevated expression level of the marker genes in a test sample as compared to a control level is indicative of a colorectal adenocarcinoma.

Description

technical field [0001] The present invention relates to an in vitro method and composition for diagnosing and / or treating adenocarcinoma associated with a chromosomal aberration of chromosome 20q and / or a tendency to develop such adenocarcinoma by determining the expression level of a set of specific marker genes, wherein the test sample Elevated marker gene expression levels compared to control levels are indicative of adenocarcinoma. Background technique [0002] Most cancers are of epithelial origin and progress progressively from normal cells, through dysplasia, to malignant cells that invade surrounding tissues and have metastatic potential. The progression of colorectal adenomas to adenocarcinomas is a classic example of this process (Muto, T. et al. (1975) Cancer 36, 2251-2270; Fearon, E.R. and Vogelstein, B. (1990) Cell 61, 759-767). Cancer of the colorectal portion of the gastrointestinal tract is a frequently occurring disease. In the first stage, benign tum...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/68A61K31/713A61K39/395
CPCC12Q2600/158C12Q2600/136C12Q2600/172C12Q2600/112C12Q2600/156C12Q1/6886A61P35/00
Inventor B.平托莫赖斯德卡瓦尔霍G.A.梅杰
Owner 基督教高等教育科学研究及病人护理协会
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