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Biomedical subjects

Jianming Pei

Publications and source records attributed to Jianming Pei.

4 recordsLinked to original sources
PubMed2006

High-resolution analysis of 9p loss in human cancer cells using single nucleotide polymorphism-based mapping arrays.

Single nucleotide polymorphism (SNP) mapping arrays were used to perform DNA copy number analysis of five human cancer cell lines (four malignant mesotheliomas; one non-small cell lung carcinoma) to identify and map the end-points of deletions of 9p. All five cell lines exhibited homozygous deletions encompassing the CDKN2A (alias INK4A/ARF) and CDKN2B loci. The DNA analysis profiles demarcated precisely two different, but overlapping, deletions in each mesothelioma cell line, but the lung cancer cells showed two copies of a single deletion. In the latter cell line, allele analysis revealed that virtually all SNPs for chromosome 9 were homozygous, suggestive of uniparental disomy. These findings demonstrate the utility of SNP-based mapping arrays for high-resolution analysis of genomic imbalances in cancer cells.

Cell Line, Tumor↗
PubMed2004

Frequent activation of AKT in non-small cell lung carcinomas and preneoplastic bronchial lesions.

AKT is frequently activated in various cancers, but its involvement in lung tumor development and progression is not well established. We examined AKT activity by immunohistochemistry in 110 non-small cell lung carcinomas (NSCLCs) using tissue microarrays. AKT activation was observed in 56 (51%) tumors. To further validate activation of the AKT pathway in this series, we examined the phosphorylation status of the mammalian target of rapamycin (mTOR) and forkhead (FKHR), two downstream targets of AKT. Positive staining for phospho-mTOR and phospho-FKHR were detected in 74% and 68% of tumors, respectively, and was significantly associated with activation of AKT. Tumors positive for phosphorylated (active) AKT were present with a similar frequency in low stage (I/II) and high stage (III/IV) tumors, raising the possibility that AKT activation occurs early in tumor progression. We therefore examined AKT activity in 25 bronchial epithelial lesions from 12 patients at high risk of lung cancer. Metaplastic/dysplastic areas showed AKT activity, whereas normal and hyperplastic bronchial epithelia exhibited little or no activity. Since some bronchial epithelial lesions may develop into invasive cancers, we examined the effect of AKT on invasiveness of lung cancer cells, using an in vitro cell invasion assay. Transfection of NSCLC cells with wild-type AKT increased invasiveness in response to hepatocyte growth factor, whereas transfection with dominant negative AKT abrogated this effect. Collectively, these data suggest that AKT activation is a frequent and early event in lung tumorigenesis, which may enhance risk of progression to malignancy. Thus, AKT represents a potentially important target for chemoprevention in individuals at high risk of NSCLC.

Adult↗
PubMed2003

High-resolution mapping of amplifications and deletions in pediatric osteosarcoma by use of CGH analysis of cDNA microarrays.

Conventional cytogenetic and comparative genomic hybridization (CGH) studies have shown that osteosarcomas (OSs) are characterized by complex structural and numerical chromosomal alterations and gene amplification. In this study, we used high-resolution CGH to investigate recurrent patterns of genomic imbalance by use of DNA derived from nine OS tumors hybridized to a 19,200-clone cDNA microarray. In six OSs, there was copy number gain or amplification of 6p, with a minimal region of gain centering on segment 6p12.1. In seven OSs, the pattern of amplification affecting chromosome arm 8q showed high-level gains of 8q12-21.3 and 8q22-q23, with amplification of the MYC oncogene at 8q24.2. Seven OSs showed copy number gain or amplification of 17p between the loci bounded by GAS7 and PMI (17p11.2-17p12), and three of these tumors also showed small losses at 17p13, including the region containing TP53. An in silico analysis of the distribution of segmental duplications (duplicons) in this region identified a large number of tracts consisting of paralogous sequences mapping to the 17p region, encompassing the region of deletions and amplifications in OS. Interestingly, within this same region there were clusters of duplicons and several genes that are expressed during bone morphogenesis and in OS. In summary, microarray CGH analysis of the chromosomal imbalances of OS confirm the overall pattern observed by use of metaphase CGH and provides a more precise refinement of the boundaries of genomic gains and losses that characterize this tumor.

Adolescent↗