Molecular profiling and comprehensive genome-wide analysis of somatic copy number alterations in gastric intramucosal neoplasias based on microsatellite status

Sugai, Tamotsu; Eizuka, Makoto; Arakawa, Noriyuki; Osakabe, Mitsumasa; Habano, Wataru; Fujita, Yuka; Yamamoto, Eiko; Yamano, Hiro‐o; Endoh, Masaki; Matsumoto, Takayuki; Suzuki, Hiromu

doi:10.1007/s10120-018-0810-5

Cited by 16 publications

(34 citation statements)

References 29 publications

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“…9 The detection loci used by many researches in Asia are different, resulting in different detection rates of MSI. 12,13 Given the existence of racial differences, study screening the optimal loci for East Asian population is lacking. In this study, the sensitivities of multiple MSI detection loci in Chinese population were compared, followed by the consistency analysis of multiple loci combinations with immunohistochemical (IHC) staining results to screen the optimal detection loci for Chinese.…”

Section: Introductionmentioning

confidence: 99%

Screening of MSI detection loci and their heterogeneity in East Asian colorectal cancer patients

Bai

Liu

et al. 2019

Cancer Medicine

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Objective This study aims to screen the MSI detection loci suitable for the East Asian colorectal cancer patients. and explore its intratumoral heterogeneity. Methods A total of 271 pathological tissues specimens of colorectal cancer were collected. The MSI status was detected using different PCR reagent kits with different detection loci. Then, the results were compared with the immunohistochemical (IHC) staining results. Microdissection of pathological tissues specimens detected to be MSI‐H was performed to examine whether there was intratumoral heterogeneity of MSI status. Results Thirty‐nine out of 271 cases were dMMR. dMMR occurred mostly in patients with right‐hemi colon cancer ( P < 0.0001). Compared with dMMR patients, the clinical stages of pMMR patients were more inclined to be in the late stage with lymph node metastasis ( P < 0.0001). MSI‐H tumors were significantly associated with KRAS mutation ( P = 0.036) and PD‐L1 expression ( P = 0.038). Compared with Promega panel and 24‐locus detection, the consistency between NCI MSI panel and IHC staining results were the highest with the Kappa value of 0.850. The sensitivity of detection decreased from 87.18% to 56.41% with the increase in detection loci. Single locus analysis showed that the first two loci with the highest sensitivity were both mononucleotide loci, namely, BAT‐26 (95.45%) and BAT‐25 (86.36%). The dinucleotide locus with highest sensitivity was D2S123 (50%). The main detection loci of MSI‐H showed no intratumoral heterogeneity. Conclusion The combination of 2 mononucleotide loci (BAT25, BAT26) and 3 dinucleotide loci (D2S123, D5S346, D17S250) might be the most suitable loci for MSI detection in East Asian population. There is no intratumoral heterogeneity in the main MSI loci.

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Section: Introductionmentioning

confidence: 99%

Screening of MSI detection loci and their heterogeneity in East Asian colorectal cancer patients

Bai

Liu

et al. 2019

Cancer Medicine

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“…Mutations in genes that regulate the cell cycle and apoptosis (e.g., TGFβ RII, IGFIIR, TCF4, RIZ, BAX, CASPASE5, FAS, BCL10, and APAF1) or maintain genomic integrity (e.g., hMSH6, hMSH3, MED1, RAD50, BLM, ATR, and MRE11) have also been associated with MSI-H GC [27]. The prevalence of GC with an MSI-high phenotype was previously shown to occur in 5-10% of sporadic GC cases, suggesting a relatively high frequency of a genomic phenotype in these types of GCs, which, in routine practice, is not a rare phenotype [25,27]. In the present study, there were signi cant differences in the frequencies of MSI and MLH-1 methylation between CRA and CDA, suggesting that MSI plays no signi cant role in CRA tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

“…MSI is considered to be an important molecular event in gastric carcinogenesis 25 and is known to result from de ciencies in the activity of mismatch repair genes (MMR genes) [27]. In sporadic GCs, MSI is caused by DNA methylation of the MLH-1 gene [27].…”

Section: Discussionmentioning

confidence: 99%

Analysis of clinicopathological and molecular features of crawling-type gastric adenocarcinoma

Fujita

Uesugi²,

Sugimoto

et al. 2020

Preprint

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Background: Crawling-type adenocarcinoma (CRA) is an important gastric cancer (GC) subtype that exhibits a specific histological pattern and has characteristic clinicopathological findings. Despite its characteristic histology, little is known about the molecular characteristics of CRA. Methods: We examined 254 GC cases, including 51 cases of CRA and 126 cases having conventional differentiated adenocarcinomas (CDAs). Results for immunohistochemistry (mucin phenotype; Muc5AC, Muc6, Muc2 and CD10, CDX-2, MLH-1, p53 and β-catenin), mutation analysis (TP53, KRAS and BRAF), microsatellite instability (BAT25, BAT26, D2S123, D5S346 and D17S250), DNA methylation status by a two-panel method (RUNX3, MINT31, LOX, NEUROG1, ELMO1 and THBD), MLH-1 promoter methylation, and allelic imbalance (AI; 1p, 3p, 4p, 5q, 8p, 9p, 13q, TP53, 18q and 22q) were examined. Results: CRAs were more likely to occur in the middle third of the stomach, in younger patients and to be macroscopically depressed. Nuclear accumulation of β-catenin and loss of MLH-1 expression were less frequent among CRA cases compared to CDA cases. At a molecular level, CRA is often characterized by the deletion mutation c.529_546 (18-base pair deletion at codon 177-182 in exon 5) in the TP53 gene (10 cases). Although the low methylation epigenotype was significantly more frequent for CRAs compared to CDAs, multiple AIs were more often seen in CRAs relative to CDAs. Conclusions: The results demonstrated that TP53 mutations, particularly c.529_546del, and multiple AIs are closely associated with CRA carcinogenesis. Our results suggest that CRA is an independent entity of GC in terms of clinicopathologic and molecular findings.

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“…DNA was extracted from isolated normal and tumor tissues by sodium dodecyl sulfate lysis and proteinase K digestion, followed by a phenol‐chloroform procedure as reported previously 18 …”

Section: Methodsmentioning

confidence: 99%

Comprehensive analysis of somatic copy number alterations in clear cell renal cell carcinoma

Tsuyukubo

Ishida

Osakabe

et al. 2020

Molecular Carcinogenesis

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Somatic copy number alterations (SCNAs) are important biological characteristics that can identify genome‐wide alterations in renal cell carcinoma (RCC). Recent studies have shown that SCNAs have potential value for determining the prognosis of RCC. We examined SCNAs using the Affymetrix platform to analyze samples from 59 patients with clear cell RCCs (ccRCCs) including first cohort (30 cases) and second cohort (validation cohort, 29 cases). We stratified SCNAs in the ccRCCs using a hierarchical cluster analysis based on SCNA types, including gain, loss of heterozygosity (LOH), copy neutral LOH, mosaic, and mixed types. In this way, the examined two cohorts were categorized into two subgroups (1 and 2). Although the frequency of mixed type was higher in subgroup 1 than in subgroup 2 in the two cohorts, the association did not reach statistical significance. There was a significant difference in the frequency of metachronous metastasis between subgroups 1 and 2 (subgroup 2 > 1). In addition, subgroup 2 was retained in multivariate analysis of both cohorts. We examined whether there were specific alleles differing between subgroups 1 and 2 in both cohorts. We found that there was indeed a statistically significant difference in the 3p mixed types. Among the 3p mixed type, we found that 3p24.3 mixed type was inversely correlated with the presence of metachronous metastasis in ccRCC. The association was also retained in multivariate analysis in second cohort. We suggest that the 3p24.3 mixed type may be a novel marker to predict a favorable prognosis in ccRCC.

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Molecular profiling and comprehensive genome-wide analysis of somatic copy number alterations in gastric intramucosal neoplasias based on microsatellite status

Cited by 16 publications

References 29 publications

Screening of MSI detection loci and their heterogeneity in East Asian colorectal cancer patients

Screening of MSI detection loci and their heterogeneity in East Asian colorectal cancer patients

Analysis of clinicopathological and molecular features of crawling-type gastric adenocarcinoma

Comprehensive analysis of somatic copy number alterations in clear cell renal cell carcinoma

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