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Characterisation of precursor lesions in colorectal cancers with DNA instability

DNA 不稳定性结直肠癌前驱病变的表征

基本信息

批准号：
nhmrc : 145005
负责人：
A/Pr Joanne Young
金额：
$ 4.01万
依托单位：
依托单位国家：
澳大利亚
项目类别：
NHMRC Project Grants
财政年份：
2001
资助国家：
澳大利亚
起止时间：
2001-01-01 至 2001-12-31
项目状态：
已结题

来源：
https://researchdata.edu.au/characterisation-precursor-lesions-dna-instability/96410
关键词：
Characterisation precursor lesions colorectal cancers

项目摘要

It is now generally accepted that most colorectal cancers arise from previously benign lesions in the mucosal lining of the large bowel. These lesions are called adenomatous polyps. They have been extensively studied as have the cancers which evolve from them with regard to the type of cancer causing genetic changes they bear. Recently, it has been found that colorectal cancer is not a single disease in that there exists a subgroup comprising 15% of colorectal cancers which is an entirely different type wwith respect to genetic changes and biological behaviour. This subgroup contains cancers with a high level of microsatellite instability (MSI-high) and the cancers which comprise this group show none of the common genetic changes which can be demonstrated in both adenomatous polyps and the 85% of colon cancers which develop from them. The MSI-high colorectal cancers do however share some striking similarities to a type of polyp (hyperplastic) which has until quite recently been considered of little consequence. Our research group and others have shown an association with colorectal cancer in those patients in whom hyperplastic polyps are unusually large or numerous, especially if present in the right side of the large bowel, where the bulk of MSI-high colorectal cancers arise. The current proposal will investigate the hyperplastic polyp as a precursor lesion in the genesis of MSI-high cancers.

现在普遍认为，大多数结直肠癌是由大肠粘膜内层的良性病变引起的。这些病变称为腺瘤性息肉。它们已经被广泛研究，就像从它们进化而来的癌症类型一样，导致它们所携带的遗传变化。最近，人们发现结直肠癌不是一种单一的疾病，因为存在一个亚组，包括15%的结直肠癌，就遗传变化和生物学行为而言，这是一种完全不同的类型。该亚组包含具有高水平微卫星不稳定性（MSI-高）的癌症，并且包括该组的癌症没有显示出在腺瘤性息肉和85%的结肠癌中可以证明的常见遗传变化。然而，MSI高的结直肠癌确实与一种息肉（增生性）有一些惊人的相似之处，直到最近才被认为没有什么后果。我们的研究小组和其他人已经表明，在那些增生性息肉异常大或多的患者中，特别是如果存在于大肠右侧，其中大部分MSI高的结直肠癌发生，与结直肠癌相关。目前的建议将研究增生性息肉作为MSI高癌症发生的前驱病变。