Author/Editor		Korošec, Branka
Title		Spremembe v genu ATP2A2 v povezavi s tumorji glave in vratu, pljuč in širokega črevesa
Translated title		Alterations in ATP2A2 gene in correlation with head and neck tumours, lung tumours and colon tumours
Type		monografija
Place		Ljubljana
Publisher		Medicinska fakulteta
Publication year		2003
Volume		str. 72
Language		slo
Abstract		Calcium release from endoplasmic reticulum in cytosol is a key component of numerous signal pathways controlling tumour growth, differentiation and cell death. Sequestration of Ca2+ in endoplasmic reticulum, from which it can be released during Ca2+ signaling events, is mediated by sarco(endo)plasmic reticulum Ca2+- ATPazes (SERCAs) Mutations in ATP2A2 gene coding sarco(endo)plasmic reticulum Ca2+- ATPaze isoform 2 cause Darier's disease in humans. An aging study using wild type and Atp2a2 +- mice revealed that heterozygous mutants have a very high incidence of squamous cell carcinomas of oral mucosa, esophageus and forestomach and papillomas in keratinized epithelial cells, the same cell type affected in human Darier disease (Liu et al.). Numerous proteins involved in mechanisms of cancer development, like K-ras and Smads, depend on intracellular calcium level. These findings and the fact that SERCA haploinsuficient mice often developed cancer led us to examine the hypothesis about the involvement and the role of ATP2A2 gene in human cancer development. To determine the role of gene ATP2A2 in human cancer development we screened patients with head and neck carcinomas, lung cancer, colon cancer and unaffected individuals for genetic alterations in ATP2A2 gene. Among 11 different alterations we found two that change amino acid, two intronic deletions, one intronic insertion, and 6 single nucleotide polymorphisms, three of them were in intronic region. The total number of novel altered alleles of all patients with different cancer was 22/574 while in unaffected (normal) population (248 alleles) we found only one of this alterations (x2 = 7,14, p = 0,01). Among eleven different alterations in nucleotide sequence the majority were germline (8/11) and only three were somatic. (Abstract truncated at 2000 characters).
Descriptors		HEAD AND NECK NEOPLASMS LUNG NEOPLASMS COLONIC NEOPLASMS CA(2+) MG(2+)-ATPASE POLYMORPHISM, SINGLE-STRANDED CONFORMATIONAL POLYMERASE CHAIN REACTION ELECTROPHORESIS, POLYACRYLAMIDE GEL BASE SEQUENCE INTRONS ALLELES DNA, NEOPLASM