Detection of kinase amplifications in gastric cancer archives using fluorescence in situ hybridization.
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.
Department of Tumor Pathology, Hamamatsu University School of Medicine, Higashi-ku, Hamamatsu, Japan.
Shin-ichiro
S
Kiyose
Kiyoko
K
Nagura
Hong
H
Tao
Hisaki
H
Igarashi
Hidetaka
H
Yamada
Masanori
M
Goto
Matsuyoshi
M
Maeda
Nobuya
N
Kurabe
Masaya
M
Suzuki
Masaru
M
Tsuboi
Tomoaki
T
Kahyo
Kazuya
K
Shinmura
Naohiko
N
Hattori
Haruhiko
H
Sugimura
D000230:Adenocarcinoma / Q000235:genetics* / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D018070:Biological Specimen Banks; D022202:Chromosomes, Artificial, Bacterial; D015331:Cohort Studies; D005240:Feasibility Studies; D005260:Female; D005784:Gene Amplification / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D008297:Male; D008875:Middle Aged; D057285:Precision Medicine; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011494:Protein Kinases / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D046888:Tissue Array Analysis
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases