SIGNIFICANCE OF CD44 GENE-PRODUCTS FOR CANCER-DIAGNOSIS AND DISEASE EVALUATION
SIGNIFICANCE OF CD44 GENE-PRODUCTS FOR CANCER-DIAGNOSIS AND DISEASE EVALUATION
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DOI：
10.1016/0140-6736(92)93077-z
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发表时间：
1992-10-31
期刊：
影响因子：
168.9
通讯作者：
TARIN, D
中科院分区：
文献类型：
--
作者：
MATSUMURA, Y;TARIN, D
随着人们越来越重视癌症的早期检测，人们正在寻找可靠的标记物，这些标记物将在临床上有助于小肿瘤的诊断和评估其转移潜力。本报告提出的证据表明，一个异常的模式的活动的CD44基因是一个有前途的候选人，这两个目的在各种类型的恶性肿瘤。通过一种被称为选择性剪接的机制，该基因可以产生不同的信使RNA分子（转录本），扩增后，这些分子在电泳凝胶中可以作为单独的条带被检测到。在瘤形成中，产生许多异常的变体转录物。以前在动物实验中发现，这样的一个变种可能是重要的转移，促使我们的研究人类肿瘤组织，良性和恶性，以及相应的正常tissues.We研究了肿瘤组织从34例肿瘤性疾病（主要是乳腺癌或结肠癌）和正常或非恶性病变的乳腺癌或结肠组织从11例患者和外周血白细胞从4名健康志愿者。用聚合酶链反应（PCR）扩增mRNA，然后电泳和印迹杂交研究CD 44基因活性。在恶性组织中，所有样本中9种或更多选择性剪接的大分子变体均出现总体过量生产，而在对照样本中，仅常规检测到标准品，偶尔检测到极少量的一种或两种小变体。此外，带型允许23例乳腺或结肠转移性肿瘤和8例未检测到转移瘤之间的区别。在血液中接种肿瘤细胞的校准研究表明，该技术可以在10（7）个白细胞中检测到10个肿瘤细胞CD44剪接变体的分析可证明不仅可应用于手术活检标本中转移潜能的早期检测，而且如果我们的发现得到证实，还可应用于容易获得的体液中，在筛查方案中对癌症进行早期诊断，评估体内残留的疾病，以及早期发现复发。
With increasing emphasis on the early detection of cancer, the search is on for reliable markers that will be clinically helpful in the diagnosis of small tumours and in the assessment of their metastatic potential. This report presents evidence that an abnormal pattern of activity of the CD44 gene is a promising candidate for both of these purposes in various types of malignancy. By a mechanism known as alternative splicing this gene can produce different messenger RNA molecules (transcripts) which are detectable, after amplification, as separate bands in electrophoretic gels. In neoplasia many abnormal variant transcripts are produced. A previous finding in animal experiments, that one such variant might be important in metastasis, prompted our study of human tumour tissue, benign and malignant, and of corresponding normal tissues.We studied tumour tissue from 34 patients with neoplastic disease (mostly breast or colon cancer) and normal or non-malignant diseased breast or colonic tissue from 11 patients and peripheral blood leucocytes from 4 healthy volunteers. CD44 gene activity was studied by amplifying messenger RNA with the polymerase chain reaction (PCR) followed by electrophoresis and blot hybridisation. In malignant tissues there was gross overproduction of each of 9 or more alternatively-spliced large molecular variants in all samples, whereas in the control samples only the standard product was routinely detected with occasional minimal quantities of one or two small variants. Furthermore, the band pattern permitted differentiation between the 23 cases with metastatic tumours of the breast or colon and the 8 with no detectable metastases. Calibration studies seeding blood with tumour cells showed that the technique can detect as few as 10 tumour cells among 10(7) leucocytes (1 ml of blood).Analysis of CD44 splice variants may prove to have applications not just to the early detection of metastatic potential in surgical biopsy specimens but also, if our findings are confirmed, in readily available bodily fluids, to the early diagnosis of cancer in screening programmes, to the assessment of remaining disease in the body and to the early detection of recurrences.