Molecular diagnosis of primary liver cancer by microsatellite DNA analysis in the serum

Abstract

Frequent loss of heterozygosity of microsatellites markers on specific chromosomal region have been reported in various types of primary human cancer. The same loss of heterozygosity has also been identified in the matched plasma/serum DNA. Using 109 microsatellite markers representing 24 chromosomal arms, we have examined the loss of heterozygosity in 21 cases of hepatocellular carcinoma, six of cholangiocarcinoma, and 27 cases of chronic hepatitis or cirrhosis. All cases of the hepatocellular carcinoma showed deletion from two to 10 chromosomal arms, while deletion of chromosomes from two to eight regions was detected in five of six cholangiocarcinoma patients. One or more loss of heterozygosity in the paired serum DNA could be detected in 16 of 25 (76.2%) hepatocellular carcinoma patients. In contrast, no alterations in serum DNA test could be found in cholangiocarcinoma patients. Five of seven (71.4%) hepatocellular carcinoma patients with alpha-fetoprotein levels less than 20 ng ml 71 produced positive serum DNA test. The profiles of 19 microsatellite markers gave a 100% positive predictive value and an 80.8% negative predictive value for hepatocellular carcinoma. In conclusion, we have determined a profile of microsatellite markers appropriate for differential diagnosis of primary liver cancer. The discovery may permit a high-throughput screening of hepatocellular carcinoma at an early stage of disease.

Microsatellite Alterations in Free-Circulating Serum DNA in Patients with Ulcerative Colitis

“…These observations were confirmed by us [18] and extended in the last years for patients with a tumor originating in the kidney [19], breast [20], head and neck [21], ovary [22], colon [23], bladder [24], and liver [25].…”

Generation of blood circulating DNA: the sources, peculiarities of circulation and structure

“…На сегодняшний день много работ посвящено изучению микросателлитных перестроек в цирДНК крови [107][108][109][110][111][112][113]. Микросателлиты -короткие повторяющиеся и высокополиморфные последовательности, состоящие из многократно повторяющегося мотива, например, ди-, три-, тетрануклеотида: (NN-N)n. Микросателлиты более или менее случайно распределены в геноме [114].…”

“…Биологическая функция микросателлитов неясна, однако они часто используются в качестве генетических маркеров для анализа расположения генов-супрессоров опухолей и т.д. Опухолеассоциированные нарушения микросателлитной ДНК были обнаружены в цирДНК плазмы крови при раке лёгких [107], головы и шеи [108], почки [109], мочевого пузыря [110], предстательной железы [111,112] и гепатоцеллюлярной карциноме [113].…”

Allelic loss of 14q32 in the pathogenesis of gastrointestinal and ampullary malignancies: mapping of the target region to a 17�cM interval

“…For example, loss of heterozygosity (LOH) on 4p, 7q, 14q, 17p, and 21q is a relatively early event in gastric carcinogenesis (Nishizuka et al 1998), while allelic losses on the 1q, 5q, 7q, 9p, 11p, 11q, 13q, 16q, 17p, and 18q may play a role in the progression of gastric carcinoma (Kim et al 2001). The frequently deleted chromosomes in biliary tract carcinoma are 4q, 5q, 9p, 14q, 17p, and 18q (Kang et al 2000;Hidaka et al 2001;Chang et al 2002).…”

“…Because each patient exhibits a distinct pattern of allelic losses in the tumor (Chang et al 2002), we screened the allelic status of synchronous ampullary carcinoma and gastric cancer in one patient on the chromosome arms 1p, 2, 3p, 4, 5, 8p, 9p, 9q, 11p, 11q, 12, 13q, 14q, 17p, 18q, and X. The clinical significance of the shared 14q deletion was analyzed on clinical cohorts of sporadic gastric and ampullary carcinoma.…”