The gene-reduction effect of chromosomal losses detected in gastric cancers

Hong, Seung‐Jin; Jeon, Eun-Jung; Oh, Jung-Hwan; Seo, Eun-Joo; Choi, Sae Kyung; Rhyu, Mun-Gan

doi:10.1186/1471-230x-10-138

Cited by 18 publications

(17 citation statements)

References 29 publications

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“…Several LOH studies demonstrated that the extent of chromosomal loss appeared to be of prognostic significance (French et al, 2004;Gazvoda et al, 2007;Koo et al, 2004). It was established that there was a trend of two distinct subtypes, high-level LOH (named LOH-H) and low-level LOH (named LOH-L), being correlated with intestinal or mixed and diffuse growth patterns, respectively (Hong et al, 2010). In our study we also found out that LOH-H was associated with intestinal type of gastric cancer .…”

Section: Lohsupporting

confidence: 65%

Genetic Instability in Gastric Cancer

Hudler¹,

Vogelsang²,

Komel³

2011

Gastric Carcinoma - Molecular Aspects and Current Advances

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Section: Lohsupporting

confidence: 65%

Genetic Instability in Gastric Cancer

Hudler¹,

Vogelsang²,

Komel³

2011

Gastric Carcinoma - Molecular Aspects and Current Advances

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“…For example, ROBO1 and ROBO2 at 3p12.3 are regulators of axon guidance, and the expression levels of these genes are frequently suppressed by methylation and/or LOH in many cancer types 38 . CADM2 39 and VGLL3 40 at 3p12.1 also have tumor suppressive functions. Collectively, these results imply that the tumor-suppressor genes at 3p12-pcen are impaired by copy-neutral LOH in DGC.…”

Section: Discussionmentioning

confidence: 99%

Identification of genomic aberrations associated with lymph node metastasis in diffuse-type gastric cancer

et al. 2018

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Diffuse-type gastric cancer (DGC) is a GC subtype with heterogeneous clinical outcomes. Lymph node metastasis of DGC heralds a dismal progression, which hampers the curative treatment of patients. However, the genomic heterogeneity of DGC remains unknown. To identify genomic variations associated with lymph node metastasis in DGC, we performed whole exome sequencing on 23 cases of DGC and paired non-tumor tissues and compared the mutation profiles according to the presence (N3, n = 13) or absence (N0, n = 10) of regional lymph node metastasis. Overall, we identified 185 recurrently mutated genes in DGC, which included a significant novel mutation at CMTM2, as well as previously known mutations at CDH1, RHOA, and TP53. Noticeably, CMTM2 expression could predict the prognostic outcomes of DGC but not intestinal-type GC (IGC), indicating pivotal roles of CMTM2 in DGC progression. In addition, we identified a recurrent loss of heterozygosity (LOH) of DNA copy numbers at the 3p12-pcen locus in DGC. A comparison of N0 and N3 tumors showed that N3 tumors exhibited more frequent DNA copy number aberrations, including copy-neutral LOH and mutations of CpTpT trinucleotides, than N0 tumors (P = 0.2 × 10−3). In conclusion, DGCs have distinct profiles of somatic mutations and DNA copy numbers according to the status of lymph node metastasis, and this might be helpful in delineating the pathobiology of DGC.

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“…On the other hand, the fixation process used for the FFPE tissues could cause DNA fragmentation, damage or fusion, thus leading to a false-negative result. Additionally, considering that loss of chromosome frequently occurred in many cancers can result in genomic chromosomal instability [ 14 – 16 ], it implies that the loss of the reference gene loci in the tumor may cause a false-positive elevated ratio of MET : AP3B1 in ddPCR, rather than high MET copy number.…”

Section: Discussionmentioning

confidence: 99%

Detection of MET Gene Copy Number in Cancer Samples Using the Droplet Digital PCR Method

Zhang¹,

Tang²,

Du³

2016

PLoS ONE

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PurposeThe analysis of MET gene copy number (CN) has been considered to be a potential biomarker to predict the response to MET-targeted therapies in various cancers. However, the current standard methods to determine MET CN are SNP 6.0 in the genomic DNA of cancer cell lines and fluorescence in situ hybridization (FISH) in tumor models, respectively, which are costly and require advanced technical skills and result in relatively subjective judgments. Therefore, we employed a novel method, droplet digital PCR (ddPCR), to determine the MET gene copy number with high accuracy and precision.MethodsThe genomic DNA of cancer cell lines or tumor models were tested and compared with the MET gene CN and MET/CEN-7 ratio determined by SNP 6.0 and FISH, respectively.ResultsIn cell lines, the linear association of the MET CN detected by ddPCR and SNP 6.0 is strong (Pearson correlation = 0.867). In tumor models, the MET CN detected by ddPCR was significantly different between the MET gene amplification and non-amplification groups according to FISH (mean: 15.4 vs 2.1; P = 0.044). Given that MET gene amplification is defined as MET CN >5.5 by ddPCR, the concordance rate between ddPCR and FISH was 98.0%, and Cohen's kappa coefficient was 0.760 (95% CI, 0.498–1.000; P <0.001).ConclusionsThe results demonstrated that the ddPCR method has the potential to quantify the MET gene copy number with high precision and accuracy as compared with the results from SNP 6.0 and FISH in cancer cell lines and tumor samples, respectively.

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The gene-reduction effect of chromosomal losses detected in gastric cancers

Cited by 18 publications

References 29 publications

Genetic Instability in Gastric Cancer

Genetic Instability in Gastric Cancer

Identification of genomic aberrations associated with lymph node metastasis in diffuse-type gastric cancer

Detection of MET Gene Copy Number in Cancer Samples Using the Droplet Digital PCR Method

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