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Methods and tools for detecting the presence of colorectal adenocarcinoma cells

A technology for rectal adenocarcinoma and colon, which is applied in the field of tumor diagnosis and can solve problems such as microsatellite instability

Inactive Publication Date: 2010-05-19
基督教高等教育科学研究及病人护理协会
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

DNA mismatch repair deficiency leading to microsatellite instability (abbreviated MSI or MIN) has been most extensively studied (diPietro et al. (2005) Gastroenterology, 129, 1047-1059), but accounts for only about 15% of glandular Tumor progresses to carcinoma

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  • Methods and tools for detecting the presence of colorectal adenocarcinoma cells
  • Methods and tools for detecting the presence of colorectal adenocarcinoma cells
  • Methods and tools for detecting the presence of colorectal adenocarcinoma cells

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0091] Example 1: Determination of the minimal overlap region within the chromosomal gain region of 20q

[0092] Selection and preparation of tumor samples

[0093] Forty-one formalin-fixed and paraffin-embedded progressive adenomas (foci of pre-existing cancer, also known as malignant polyps) and 73 snap-frozen Colorectal neoplasms (37 non-progressed adenomas and 36 cancers). All samples were used in compliance with institutional ethical regulations.

[0094] The 41 malignant polyps (archival material) corresponded to 38 patients (19 females and 19 males), as 3 patients presented with more than one malignant polyp. The mean age of patients was 67 years (range 45-86 years). From these polyps, the adenoma and carcinoma components were analyzed separately, adding a total of 82 archival samples (41x2) analyzed.

[0095] The 73 frozen samples corresponded to 65 patients (31 females and 34 males). Of these, 6 patients had multiple neoplasms: 4 patients, multiple adenomas and ...

Embodiment 2

[0120] Example 2: Microarray expression analysis

[0121] To investigate the impact of chromosomal instability on gene expression in colorectal adenoma-to-carcinoma progression, the entire genome was analyzed by array-CGH in a series of 68 colorectal tumors (37 non-progressive adenomas and 31 carcinomas) Copy number changes, and expression levels were analyzed by microarray analysis. For the most frequently occurring type of chromosomal abnormality, 20q gain, a putative oncogene with a role in the progression of colorectal cancer was identified.

[0122] In Table 2, an overview of the genes located within the SROs of Table 1 is provided when comparing colorectal adenoma and adenocarcinoma tissues, as determined by microarray analysis of mRNA from biopsy or resection samples, They were found to have significantly different expression (FDR<0,1 (false rate of determination)).

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Abstract

The present invention discloses methods and tools for reliably detecting the presence of adenocarcinoma cells in a patient, at the genetic level. The present invention fine-maps the regions of chromosomal aberrations linked to progression of adenomas into adenocarcinoma cells and provides methods and tools for detection based thereon.

Description

field of invention [0001] The present invention relates to methods for tumor diagnosis, more specifically for detecting the presence of colorectal adenocarcinoma. The invention further provides primers and probes for performing these methods. Background of the invention [0002] Cancer of the colorectal portion of the gastrointestinal tract is a frequently occurring disorder. In the first stage, benign tumors (adenomas) develop, which can turn into malignant cancers (adenocarcinomas). Not all adenomas progress to carcinoma. In fact this progression to carcinoma occurs only in a small fraction of tumors. The initiation of genomic instability is a critical step and occurs in two ways in colorectal cancer (Lengauer et al. (1998) Nature, 396, 643-649). DNA mismatch repair deficiency leading to microsatellite instability (abbreviated MSI or MIN) has been most extensively studied (diPietro et al. (2005) Gastroenterology, 129, 1047-1059), but accounts for only about 15% of glan...

Claims

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Application Information

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IPC IPC(8): C12Q1/68
CPCC12Q2600/16C12Q1/6886C12Q2600/118
Inventor G·A·梅杰B·平托莫赖斯德卡瓦尔霍
Owner 基督教高等教育科学研究及病人护理协会
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