Profiling Lung Cancer Mutations Using Oligo aCGH
Profiling Lung Cancer Mutations Using Oligo aCGH
A review of High-resolution genomic profiles of human lung cancer.
Note: This is a review of the published article listed below. All information, quotes, figures, methods, and findings mentioned in this review are from that article, and are the property of its authors and/or the publication in which the article originally appeared.
The work of Tonon, et al (2005) underscores the effectiveness of oligo aCGH technology in characterizing genes related to lung cancer tumor progression. The group uses Agilent’s Oligo aCGH microarrays to establish an integrated high-resolution survey of regional amplifications and deletions, coupled with gene-expression profiling of non-small-cell lung cancer subtypes, adenocarcinoma and squamous-cell carcinoma (SCC). This groundbreaking research demonstrates the efficacy of using gene-specific CGH platforms, custom bioinformatics tools, and integration of expression profiles to identify many recurrent amplifications and deletions in the non-small-cell lung cancer (NSCLC) genome. This work suggests that a large number of important oncogenes and tumor-suppressor genes remain to be identified, opening potential therapeutic and diagnostic opportunities for this disease.
Figure 1. Genomic profiles of primary lung AC and squamous carcinomas and lung cancer cell lines.
(Upper) Recurrence of chromosomal alterations. Integer-value recurrence of chromosomal numerical aberrations (CNAs) in segmented data (y axis) is plotted for each probe evenly aligned along the x axis in chromosome order. Dark red or green bars denote gain or loss of chromosome material, and bright red or green bars represent probes within regions of amplification or deletion. Asterisks identify the most frequent region of gains (red) and losses (green), as reported in ref. 7. (Lower) Heat-map plot showing discrete CNAs within all samples, with the x axis representing probes ordered by genomic map positions and the y axis representing individual samples. Red represents chromosomal gain/amplification, and green denotes chromosomal loss/deletion.
Figure 2. Chromosome 3q, from 180 to 199 Mb, is the only genomic region that shows a significant difference between AC and SCC by both aCGH (A) and expression (B) profiling. On both plots, x-axis coordinates represent probes ordered by genomic map positions, from chromosome 1 to chromosome X.
(A) Probes significantly gained/amplified, comparing SCC and AC primary tumors, on aCGH. The y axis represents the -log10 p value of the permutation test. Probes presenting a p < 0.05 are plotted in red, and probes with a p > 0.05 are plotted in gray. No probes were significantly lost/deleted after comparison between SCC and AC primary tumors. (B) Genomic regions significantly enriched for differentially expressed probes comparing SCC and AC primary tumors. The y axis represents the -log10 adjusted p values of Fisher's exact test for enrichment. Red lines highlight regions with a p < 0.05, adjusted for multiple testing, and probes with an adjusted p > 0.05 are in gray.
Title: High-resolution genomic profiles of human lung cancer.
Authors: Tonon G, Wong KK, Maulik G, Brennan C, Feng B, Zhang Y, Khatry DB, Protopopov A, You MJ, Aguirre AJ, Martin ES, Yang Z, Ji H, Chin L, Depinho RA.
Journal: Proc Natl Acad Sci U S A. 2005 Jul 5;102(27):9625-30. Epub 2005 Jun 27.
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