Mutational analysis of hypoxia-related genes HIF1α and CUL2 in common human cancers
作者： SANG WOOK PARK , NAK GYUN CHUNG , SOO YOUNG HUR , HO SHIK KIM , NAM JIN YOO
DOI: 10.1111/J.1600-0463.2009.02550.X
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摘要: Biochemistry, College of Medicine,The Catholic University Korea, Seoul, KoreaPark SW, Chung NG, Hur SY, Kim HS, Yoo NJ, Lee SH. Mutational analysis hypoxia-relatedgenes HIF1a and CUL2 in common human cancers. APMIS 2009; 117: 880–5.Hypoxia is a general feature solid cancer tissues. Hypoxia upregulates hypoxia-inducible factor 1a(HIF1a) that transactivates downstream genes contributes to pathogenesis. upreg-ulated not only by hypoxia but also genetic alterations HIF1a-related genes, including VHL.Cullin 2 (CUL2) interacts with the trimeric VHL-elongin B-elongin C complex plays an essentialrole ubiquitinated degradation HIF1a. The aim this study was explore whether HIF1aand are somatically mutated, contribute activation can-cers. For this, we have analyzed coding region oxygen-dependent domain HIF1ain 47 colon, gastric, breast, lung, hepatocellular carcinomas, acute leukemias bya single-strand conformation polymorphism assay. In addition, mononucleotide repeatsequences (A8) 55 colorectal 45 gastric carcinomas microsatellite instability(MSI). We found one mutation (p.Ala593Pro) (1⁄47; 2.1%),but none other two frameshift mutations colon cancers (p.Asn292MetfsX20), which were exclusively detected high MSI (4.9%; 2⁄41). Our data indicate thatsomatic rare cancers, somatic occurs frac-tion (colorectal MSI). suggest neither norCUL2 may play central role colorectal, lung andhepatocellular leukemias.Key words: HIF1a; CUL2; hypoxia; mutation; cancer; instability.Sug Hyung Lee, Department Pathology, Medicine, Korea,505 Banpo-dong, Socho-gu, Seoul 137 701, Korea. e-mail: suhulee@catholic.ac.kr*
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