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Detection of kinase amplifications in gastric cancer archives using fluorescence in situ hybridization
Authors:Kiyose Shin-ichiro  Nagura Kiyoko  Tao Hong  Igarashi Hisaki  Yamada Hidetaka  Goto Masanori  Maeda Matsuyoshi  Kurabe Nobuya  Suzuki Masaya  Tsuboi Masaru  Kahyo Tomoaki  Shinmura Kazuya  Hattori Naohiko  Sugimura Haruhiko
Affiliation:Department of Tumor Pathology, Hamamatsu University School of Medicine, Higashi-ku, Hamamatsu, Japan.
Abstract:To test the feasibility of using bacterial artificial chromosomes (BAC) containing kinases for pathological diagnosis using fluorescence in situ hybridization (FISH), 10 BAC probes containing a gene amplified in 5% or more of a pilot cohort were selected from a previous survey using arbitrarily selected BAC clones harboring 100 kinases. In this report, we describe the prevalence and association with the clinicopathological profile of these selected 10 BAC probes in 365 gastric cancer tissues. FISH analyses using these 10 BAC probes containing loci encoding EGFR, ERBB2(HER2), EPHB3, PIK3CA, MET, PTK7, ACK1, STK15, SRC, and HCK showed detectable amplifications in paraffin-embedded tissue in 2.83% to 13.6% of the gastric cancer tissues. Considerable numbers of the cases showed the co-amplification of two or more of the probes that were tested. BAC probes located within a genome neighborhood, such as PIK3CA, EPHB3, and ACK1 at 3q26-29 or HCK, SRC, and STK15 at 20q11-13.1, were often co-amplified in the same cases, but non-random co-amplifications of genes at distant genomic loci were also observed. These findings provide basic information regarding the creation of a strategy for personalizing gastric cancer therapy, especially when using multiple kinase inhibitors.
Keywords:amplification  companion diagnosis  fluorescence in situ hybridization  kinase  kinase inhibitor
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