Detection of kinase amplifications in gastric cancer archives using fluorescence in situ hybridization

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.

Detection of kinase amplifications in gastric adenocarcinomas

“…Therefore, our data also supported the possible responsibility of chromosome 7 polysomy for increased EGFR gene copy number in gastric carcinomas. The range of the MET gene amplification prevalence was between 3% and 30%, (17,25,26), but it was interesting that a relatively higher rate was determined in our series. Because of the higher rate, the samples were analyzed twice.…”

“…However, there is a lack of detailed information about the formation of the gene amplifications and their status in tissues. Kiyose et al (17) stated that the gene amplifications may be the cause of tumor progression, or they may be inducers of severe structural changes in the genome. EGFR amplification has been described in many human tumors, including gastric cancer.…”

Chemotherapy for Gastric Cancer — What Comes Next?

“…The co-occurring expression of targets is a case of being ERBB2 and PIK3CA in breast cancer [32]. With regard to GC, although KRAS mutations are initially recognized as an infrequent phenomenon in GC [33], the alterations and amplifications of other genes --both known or previously unreported--have been subsequently found in a substantial number of GC patients in a mutually exclusive manner [34,35] or co-amplified manner [36]. These findings create a challenge in the treatment regimen with either a use of each blockade of each targetable molecule or a use of dual-or paninhibitors of kinases [37].…”

A novel prognostic marker of non-small cell lung cancer: chromosome 9 open reading frame 86 (C9orf86)

“…To date, we are able to utilize a number of prognostic indicators using human genome information and molecular technologies that: range from classical histopathological classification to somatic genetic changes (mutations, amplification, translocations and deletions) (2)(3)(4). Recently, Peng and colleagues have suggested a novel prognostic marker in patients with nonsmall cell lung cancer (NSCLC): overexpression of the chromosome 9 open reading frame 86 (C9orf86) gene (5).…”