TY - JOUR
T1 - Mutation analysis of the PTEN/MMAC1 gene in lung cancer
AU - Forgacs, Eva
AU - Biesterveld, Eric J.
AU - Sekido, Yoshitaka
AU - Fong, Kwun
AU - Muneer, Sabeeha
AU - Wistuba, Ignacio I.
AU - Milchgrub, Sara
AU - Brezinschek, Ruth
AU - Virmani, Arvind
AU - Gazdar, Adi F.
AU - Minna, John D.
N1 - Funding Information:
We thank Craig Kamibayashi for helpful discussions in preparation of this manuscript. Supported by National Cancer Institute Lung Cancer SPORE grant P50 CA70907 and the G Harold and Leila Y Mathers Charitable Foundation. EJB and SM are part of the UTSW Cell Regulation graduate program.
PY - 1998/9/24
Y1 - 1998/9/24
N2 - We studied PTEN/MMAC1, a newly discovered candidate tumor suppressor gene at 10q23.3, for mutations in lung cancer. One hundred and thirty-six lung cancer cell line DNAs (66 small cell lung cancers, SCLC, 61 non-small cell lung cancers, NSCLC, four mesotheliomas, five extrapulmonary small cell cancers) were analysed for PTEN/MMAC1 homozygous deletions and five (8%) SCLC lines showed homozygous deletions interrupting the PTEN/MMAC1 gene. Using single stranded conformation polymorphism (SSCP) analysis, we screened the PTEN/MMAC1 open reading frame of 53 lung cancer cell line cDNAs for point mutations and found that 3/35 SCLCs and 3/18 NSCLCs contained homozygous amino acid sequence altering mutations. Northern blot analysis revealed that expression of the PTEN/MMAC1 gene was considerably lower in all the tumor cell lines with point mutations while no expression was detected for cell lines with PTEN/MMAC1 homozygous deletions. Mutation analysis of 22 uncultured, microdissected, primary SCLC tumors and metastases showed two silent mutations, and two apparent homozygous deletions. We also discovered a processed pseudogene (PTEN2) which has 98.5% nt identity to PTEN/MMAC1, that needs to be accounted for in cDNA mutation analysis. Our findings suggest that genetic abnormalities of the PTEN/MMAC1 gene are only involved in a relatively small subset of lung cancers.
AB - We studied PTEN/MMAC1, a newly discovered candidate tumor suppressor gene at 10q23.3, for mutations in lung cancer. One hundred and thirty-six lung cancer cell line DNAs (66 small cell lung cancers, SCLC, 61 non-small cell lung cancers, NSCLC, four mesotheliomas, five extrapulmonary small cell cancers) were analysed for PTEN/MMAC1 homozygous deletions and five (8%) SCLC lines showed homozygous deletions interrupting the PTEN/MMAC1 gene. Using single stranded conformation polymorphism (SSCP) analysis, we screened the PTEN/MMAC1 open reading frame of 53 lung cancer cell line cDNAs for point mutations and found that 3/35 SCLCs and 3/18 NSCLCs contained homozygous amino acid sequence altering mutations. Northern blot analysis revealed that expression of the PTEN/MMAC1 gene was considerably lower in all the tumor cell lines with point mutations while no expression was detected for cell lines with PTEN/MMAC1 homozygous deletions. Mutation analysis of 22 uncultured, microdissected, primary SCLC tumors and metastases showed two silent mutations, and two apparent homozygous deletions. We also discovered a processed pseudogene (PTEN2) which has 98.5% nt identity to PTEN/MMAC1, that needs to be accounted for in cDNA mutation analysis. Our findings suggest that genetic abnormalities of the PTEN/MMAC1 gene are only involved in a relatively small subset of lung cancers.
KW - Chromosome 10q23
KW - Homozygous deletion
KW - Loss of heterozygosity
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U2 - 10.1038/sj.onc.1202070
DO - 10.1038/sj.onc.1202070
M3 - Article
C2 - 9794233
AN - SCOPUS:7844247587
SN - 0950-9232
VL - 17
SP - 1557
EP - 1565
JO - Oncogene
JF - Oncogene
IS - 12
ER -