Xiaojun Zhao
CancerLoss of heterozygosityLung cancerGeneticsBiology
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Publications 20
#1Derek Y. Chiang (MIT: Massachusetts Institute of Technology)H-Index: 37
#2Gad Getz (MIT: Massachusetts Institute of Technology)H-Index: 137
Last. Eric S. Lander (MIT: Massachusetts Institute of Technology)H-Index: 252
view all 10 authors...
Massively parallel sequencing is a precise way to analyze copy-number variations given the right computational tools. An algorithm now facilitates the detection and fine mapping of copy-number gains and losses from millions of short sequence reads.
444 CitationsSource
#1Li Ding (WashU: Washington University in St. Louis)H-Index: 88
#2Gad Getz (Broad Institute)H-Index: 137
Last. Richard K. Wilson (WashU: Washington University in St. Louis)H-Index: 156
view all 90 authors...
Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus ar...
1,857 CitationsSource
#1Jussi Koivunen (Harvard University)H-Index: 16
#2Jhingook Kim (SKKU: Sungkyunkwan University)H-Index: 48
Last. Pascal Janne (Harvard University)H-Index: 112
view all 16 authors...
Somatic mutations of LKB1 tumour suppressor gene have been detected in human cancers including non-small cell lung cancer (NSCLC). The relationship between LKB1 mutations and clinicopathological characteristics and other common oncogene mutations in NSCLC is inadequately described. In this study we evaluated tumour specimens from 310 patients with NSCLC including those with adenocarcinoma, adenosquamous carcinoma, and squamous cell carcinoma histologies. Tumours were obtained from patients of US...
106 CitationsSource
#1Jeffrey A. Engelman (Harvard University)H-Index: 92
#2Kreshnik Zejnullahu (Harvard University)H-Index: 12
Last. Pascal Janne (Harvard University)H-Index: 112
view all 16 authors...
1 CitationsSource
#1Jeffrey A. Engelman (Harvard University)H-Index: 92
#2Kreshnik Zejnullahu (Harvard University)H-Index: 12
Last. Pascal Janne (Harvard University)H-Index: 112
view all 19 authors...
The epidermal growth factor receptor (EGFR) kinase inhibitors gefitinib and erlotinib are effective treatments for lung cancers with EGFR activating mutations, but these tumors invariably develop drug resistance. Here, we describe a gefitinib-sensitive lung cancer cell line that developed resistance to gefitinib as a result of focal amplification of the MET proto-oncogene. inhibition of MET signaling in these cells restored their sensitivity to gefitinib. MET amplification was detected in 4 of 1...
3,238 CitationsSource
#1Rameen BeroukhimH-Index: 95
#2Ming LinH-Index: 8
Last. Cheng LiH-Index: 56
view all 16 authors...
7 CitationsSource
#1Jeffrey A. Engelman (Harvard University)H-Index: 92
#2Toru Mukohara (Harvard University)H-Index: 3
Last. Pascal Janne (Harvard University)H-Index: 112
view all 16 authors...
EGFR is frequently mutated and amplified in lung adenocarcinomas sensitive to EGFR inhibitors gefitinib and erlotinib. A secondary mutation, T790M, has been associated with acquired resistance but has not been shown to be sufficient to render EGFR mutant/amplified lung cancers resistant to EGFR inhibitors. We created a model for studying acquired resistance to gefitinib by prolonged exposure of a gefitinib-sensitive lung carcinoma cell line (H3255; EGFR mutated and amplified) to gefitinib in vit...
366 CitationsSource
#1Torstein Tengs (Broad Institute)H-Index: 7
#2Jeffrey C. Lee (Broad Institute)H-Index: 23
Last. Roman K. Thomas (MPG: Max Planck Society)H-Index: 64
view all 7 authors...
We have designed resequencing microarrays to test the performance of this platform when interrogating a large number of exons (164 total) from genes associated with cancer. To evaluate false positive and negative rates, dideoxy sequencing was done for 335,420 bases interrogated by the arrays. From the array data, calls could be made for w97.5% of the bases, and false positive rates were very low with only a single mutation reported from the array dataset for which the corresponding dideoxy trace...
30 CitationsSource
#1Hongbin Ji (Harvard University)H-Index: 46
#2Xiaojun Zhao (Harvard University)H-Index: 16
Last. Kwok-Kin Wong (Broad Institute)H-Index: 84
view all 24 authors...
The tyrosine kinase inhibitors gefitinib (Iressa) and erlotinib (Tarceva) have shown anti-tumor activity in the treatment of non-small cell lung cancer (NSCLC). Dramatic and durable responses have occurred in NSCLC tumors with mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR). In contrast, these inhibitors have shown limited efficacy in glioblastoma, where a distinct EGFR mutation, the variant III (vIII) in-frame deletion of exons 2–7, is commonly found. In t...
221 CitationsSource
#1Rameen Beroukhim (Brigham and Women's Hospital)H-Index: 95
#2Ming Lin (Harvard University)H-Index: 8
Last. Cheng Li (Harvard University)H-Index: 56
view all 16 authors...
Loss of heterozygosity (LOH) of chromosomal regions bearing tumor suppressors is a key event in the evolution of epithelial and mesenchymal tumors. Identification of these regions usually relies on genotyping tumor and counterpart normal DNA and noting regions where heterozygous alleles in the normal DNA become homozygous in the tumor. However, paired normal samples for tumors and cell lines are often not available. With the advent of oligonucleotide arrays that simultaneously assay thousands of...
149 CitationsSource