A comprehensive search for DNA amplification in lung cancer identifies inhibitors of apoptosis cIAP1 and cIAP2 as candidate oncogenes.
Amplification of oncogenes is an important mechanism that can cause gene overexpression and contributes to tumor development. The identification of amplified regions might have both prognostic and therapeutic significance. We used primary lung carcinomas and lung cancer cell lines for restriction landmark genomic scanning (RLGS) to identify novel amplified sequences. Enhanced RLGS fragments that indicate gene amplification were observed in primary tumors and lung cancer cell lines of both non-small cell lung cancer and small cell lung cancer. We identified one novel amplicon on chromosome 11q22, in addition to previously reported amplicons that include oncogenes MYCC, MYCL1 and previously identified amplification of chromosomal regions 6q21 and 3q26-27. Amplification of 11q22 has been reported in other types of cancer and was refined to an approximately 1.19 Mbp region for which the complete sequence is available. Based on a patient sample with a small region of low-level amplification we were able to further narrow this region to 0.92 Mbp. Genes localized in this region include two inhibitors of apoptosis (cIAP1 and cIAP2). Immunohistochemistry and western blot analysis identified cIAP1 and cIAP2 as potential oncogenes in this region as both are overexpressed in multiple lung cancers with or without higher copy numbers.
Dai
Zunyan
Z
Program of Human Cancer Genetics, Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, OH, 43210, USA.
Zhu
Wei-Guo
WG
Morrison
Carl D
CD
Brena
Romulo M
RM
Smiraglia
Dominic J
DJ
Raval
Aparna
A
Wu
Yue-Zhong
YZ
Rush
Laura J
LJ
Ross
Patrick
P
Molina
Julian R
JR
Otterson
Gregory A
GA
Plass
Christoph
C
D015139:Blotting, Southern; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics; D045744:Cell Line, Tumor; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002880:Chromosomes, Human, Pair 11; D002893:Chromosomes, Human, Pair 3; D002896:Chromosomes, Human, Pair 6; D003001:Cloning, Molecular; D004247:DNA / Q000096:biosynthesis* / Q000378:metabolism; D004262:DNA Restriction Enzymes / Q000494:pharmacology; D020224:Expressed Sequence Tags; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism*; D008957:Models, Genetic; D014176:Protein Biosynthesis; D011506:Proteins / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases
D051034:Inhibitor of Apoptosis Proteins; D011506:Proteins; D004247:DNA; C494833:BIRC2 protein, human; D044767:Ubiquitin-Protein Ligases; D004262:DNA Restriction Enzymes