Biomedical subjects

Tzu-Hsiu Chen

Publications and source records attributed to Tzu-Hsiu Chen.

6 recordsLinked to original sources

PubMed2006

Sensitive mutation detection in heterogeneous cancer specimens by massively parallel picoliter reactor sequencing.

The sensitivity of conventional DNA sequencing in tumor biopsies is limited by stromal contamination and by genetic heterogeneity within the cancer. Here, we show that microreactor-based pyrosequencing can detect rare cancer-associated sequence variations by independent and parallel sampling of multiple representatives of a given DNA fragment. This technology can thereby facilitate accurate molecular diagnosis of heterogeneous cancer specimens and enable patient selection for targeted cancer therapies.

Base Sequence↗

PubMed2005

Oncogenic transformation by inhibitor-sensitive and -resistant EGFR mutants.

BACKGROUND: Somatic mutations in the kinase domain of the epidermal growth factor receptor tyrosine kinase gene EGFR are common in lung adenocarcinoma. The presence of mutations correlates with tumor sensitivity to the EGFR inhibitors erlotinib and gefitinib, but the transforming potential of specific mutations and their relationship to drug sensitivity have not been described. METHODS AND FINDINGS: Here, we demonstrate that EGFR active site mutants are oncogenic. Mutant EGFR can transform both fibroblasts and lung epithelial cells in the absence of exogenous epidermal growth factor, as evidenced by anchorage-independent growth, focus formation, and tumor formation in immunocompromised mice. Transformation is associated with constitutive autophosphorylation of EGFR, Shc phosphorylation, and STAT pathway activation. Whereas transformation by most EGFR mutants confers on cells sensitivity to erlotinib and gefitinib, transformation by an exon 20 insertion makes cells resistant to these inhibitors but more sensitive to the irreversible inhibitor CL-387,785. CONCLUSION: Oncogenic transformation of cells by different EGFR mutants causes differential sensitivity to gefitinib and erlotinib. Treatment of lung cancers harboring EGFR exon 20 insertions may therefore require the development of alternative kinase inhibition strategies.

Adaptor Proteins, Signal Transducing↗

PubMed2004

An integrated view of copy number and allelic alterations in the cancer genome using single nucleotide polymorphism arrays.

Changes in DNA copy number contribute to cancer pathogenesis. We now show that high-density single nucleotide polymorphism (SNP) arrays can detect copy number alterations. By hybridizing genomic representations of breast and lung carcinoma cell line and lung tumor DNA to SNP arrays, and measuring locus-specific hybridization intensity, we detected both known and novel genomic amplifications and homozygous deletions in these cancer samples. Moreover, by combining genotyping with SNP quantitation, we could distinguish loss of heterozygosity events caused by hemizygous deletion from those that occur by copy-neutral events. The simultaneous measurement of DNA copy number changes and loss of heterozygosity events by SNP arrays should strengthen our ability to discover cancer-causing genes and to refine cancer diagnosis.

Alleles↗

PubMed2004

High-resolution single-nucleotide polymorphism array and clustering analysis of loss of heterozygosity in human lung cancer cell lines.

Chromosomal loss of heterozygosity (LOH) is a common mechanism for the inactivation of tumor suppressor genes in human epithelial cancers. Hybridization to single-nucleotide polymorphism (SNP) arrays is an efficient method to detect genome-wide cancer LOH. Here, we survey LOH patterns in a panel of 33 human lung cancer cell lines using SNP array hybridization containing 1500 SNPs. We compared the LOH patterns generated by SNP array hybridization to those previously obtained by 399 microsatellite markers and find a high degree of concordance between the two methods. A novel informatics platform, dChipSNP, was used to perform hierarchical tumor clustering based on genome-wide LOH patterns. We demonstrate that this method can separate non-small-cell and small-cell lung cancer samples based on their shared LOH. Furthermore, we analysed seven human lung cancer cell lines using a novel 10 000 SNP array and demonstrate that this is an efficient and reliable method of high-density allelotyping. Using this array, we identified small regions of LOH that were not detected by lower density SNP arrays or by standard microsatellite marker panels.

Biomarkers, Tumor↗

PubMed2002

Missense mutations of the BRAF gene in human lung adenocarcinoma.

Mutations of the BRAF protein serine/threonine kinase gene have recently been identified in a variety of human cancers, most notably melanomas. We sought to determine the frequency of BRAF mutations in human lung cancer pathogenesis. Analysis of BRAF sequence from 127 primary human lung adenocarcinomas revealed mutations in two tumor specimens, one in exon 11 (G465V), and a second in exon 15 (L596R). These specimens belong to the same adenocarcinoma subgroup as defined by clustering of gene expression data. BRAF may provide a target for anticancer chemotherapy in a subset of lung adenocarcinoma patients.

Adenocarcinoma↗

PubMed2000

TT viral infection through blood transfusion: retrospective investigation on patients in a prospective study of post-transfusion hepatitis.

AIM:To investigate the role of blood transfusion in TT viral infection(TTV).METHODS:We retrospectively studied serum samples from 192 transfusion recipients who underwent cardiovascular surgery and blood transfusion between July 1991 and June 1992. All patients had a follow-up every other week for at least 6 months after transfusion. Eighty recipients received blood before screening donors for hepatitis C antibody (anti-HCV), and 112 recipients received screened blood. Recipients with alanine aminotransferase level > 2.5 times the upper normal limit were tested for serological markers for viral hepatitis A, B, C, G, Epstein-Barr virus and cytomegalovirus. TTV infection was defined by the positivity for serum TTV DNA using the polymerase chain reaction method.RESULTS: Eleven and three patients, who received anti-HCV unscreened and screened blood, respectively, had serum ALT levels > 90IU/L. Five patients (HCV and TTV 1; HCV, HGV, and TTV 1; TTV 2; and CMV and TTV 1) were positive for TTV DNA, and four of them had sero conversion of TTV DNA.CONCLUSION:TTV can be transmitted via blood transfusion.Two recipients infected by TTV alone may be associated with the hepatitis. However, whether TTV was the causal agent remains unsettled, and further studies are necessary to define the role of TTV infection in chronic hepatitis.

Journal Article↗