PURPOSE: To explore intratumor heterogeneity in gene expression profiles from patients with cervical cancer. EXPERIMENTAL DESIGN: A total of 33 biopsies were obtained from 11 patients, sampling between two and five different areas for each tumor. The extracted RNA was hybridized onto the Affymetrix U133 Plus 2.0 oligonucleotide chip. The variance of expression within a patient (W), between patients (B) and the total variance (T = W + B) were calculated for each ProbeSet, and the ratio W/T was used as a measure of intratumor heterogeneity. Gene Ontology functional analysis was done to assess the function of genes that had high W/T (top 10%) and low W/T (bottom 10%) values. RESULTS: In total, 448 ProbeSets (2.2% of the total) had W/T < 0.10, indicating low intratumor heterogeneity, and 537 ProbeSets (2.7% of the total) had W/T > 0.90, indicating high intratumor heterogeneity. In total 14,473 ProbeSets (72.4%) had higher intertumor than intratumor heterogeneity (W/T < 0.5). Genes with low intratumor heterogeneity were characterized by a statistically significant enrichment of immune-related functions (P < 0.0001). Genes with high intratumor heterogeneity were characterized by a significant tendency towards nuclear localization and nucleic acid binding (both P < 0.0001). For genes with W/T > 0.5, more than six biopsies would be required to minimize the intratumoral heterogeneity to <0.15; if W/T is 0.3 to 0.4, four biopsies are required; and for low W/T of 0.16 to 0.3, only two to three biopsies would be needed. CONCLUSION: Although the intratumor heterogeneity was low for the majority of the tested ProbeSets, for many genes, multiple biopsies are required to obtain a reliable estimate of gene expression.
PURPOSE: To explore intratumor heterogeneity in gene expression profiles from patients with cervical cancer. EXPERIMENTAL DESIGN: A total of 33 biopsies were obtained from 11 patients, sampling between two and five different areas for each tumor. The extracted RNA was hybridized onto the Affymetrix U133 Plus 2.0 oligonucleotide chip. The variance of expression within a patient (W), between patients (B) and the total variance (T = W + B) were calculated for each ProbeSet, and the ratio W/T was used as a measure of intratumor heterogeneity. Gene Ontology functional analysis was done to assess the function of genes that had high W/T (top 10%) and low W/T (bottom 10%) values. RESULTS: In total, 448 ProbeSets (2.2% of the total) had W/T < 0.10, indicating low intratumor heterogeneity, and 537 ProbeSets (2.7% of the total) had W/T > 0.90, indicating high intratumor heterogeneity. In total 14,473 ProbeSets (72.4%) had higher intertumor than intratumor heterogeneity (W/T < 0.5). Genes with low intratumor heterogeneity were characterized by a statistically significant enrichment of immune-related functions (P < 0.0001). Genes with high intratumor heterogeneity were characterized by a significant tendency towards nuclear localization and nucleic acid binding (both P < 0.0001). For genes with W/T > 0.5, more than six biopsies would be required to minimize the intratumoral heterogeneity to <0.15; if W/T is 0.3 to 0.4, four biopsies are required; and for low W/T of 0.16 to 0.3, only two to three biopsies would be needed. CONCLUSION: Although the intratumor heterogeneity was low for the majority of the tested ProbeSets, for many genes, multiple biopsies are required to obtain a reliable estimate of gene expression.
Authors: Paul C Boutros; Suzanne K Lau; Melania Pintilie; Ni Liu; Frances A Shepherd; Sandy D Der; Ming-Sound Tsao; Linda Z Penn; Igor Jurisica Journal: Proc Natl Acad Sci U S A Date: 2009-02-05 Impact factor: 11.205
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Authors: Philippe Lambin; Ruud G P M van Stiphout; Maud H W Starmans; Emmanuel Rios-Velazquez; Georgi Nalbantov; Hugo J W L Aerts; Erik Roelofs; Wouter van Elmpt; Paul C Boutros; Pierluigi Granone; Vincenzo Valentini; Adrian C Begg; Dirk De Ruysscher; Andre Dekker Journal: Nat Rev Clin Oncol Date: 2012-11-20 Impact factor: 66.675
Authors: Nicholas Navin; Alexander Krasnitz; Linda Rodgers; Kerry Cook; Jennifer Meth; Jude Kendall; Michael Riggs; Yvonne Eberling; Jennifer Troge; Vladimir Grubor; Dan Levy; Pär Lundin; Susanne Månér; Anders Zetterberg; James Hicks; Michael Wigler Journal: Genome Res Date: 2009-11-10 Impact factor: 9.043