Chromosome 7 Multiplication in EGFR-positive Lung Carcinomas Based on Tissue Microarray Analysis

Tsiambas, Evangelos; Mastronikolis, Nicholas; Lefas, Alicia Y; Georgiannos, Stavros N; Ragos, Vasileios; Fotiades, Panagiotis P; Tsoukalas, Nikolaos; Kavantzas, Nikolaos; Karameris, Andreas; Peschos, Dimitrios; Patsouris, Efstratios; Syrigos, Konstantinos

doi:10.21873/invivo.11106

Cited by 5 publications

(1 citation statement)

References 40 publications

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“…Both of these genes are found on the short arm of Chromosome 7 where fifteen other transcriptionally dysregulated genes were identified suggesting the region is specifically important in EGFR activated lung cancer. Recent reports implicate the region in LUAD [28, 29].…”

Section: Discussionmentioning

confidence: 99%

Modulation of proliferation factors in lung adenocarcinoma with an analysis of the transcriptional consequences of genomic EGFR activation

Kucherlapati

2019

Oncotarget

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Genes of the pre-replication, pre-initiation and replisome complexes duplicate the genome from many sites once in a normal cell cycle. This study examines complex components in lung adenocarcinoma (LUAD) closely, correlating changes in the genome and transcriptome with proliferation and overall survival. Molecular subtypes (The Cancer Genome Atlas (TCGA), 2014) based on copy number, DNA methylation, and mRNA expression had variable proliferation levels, the highest correlating with decreased survival. A pattern of increased expression typified by POLE2 and POLQ was found for multiple replication factors over thirty-seven tumor types. EGFR altered cases unanticipatedly inversely correlated with proliferation factor expression in LUAD, Colon adenocarcinoma, and Cancer Cell Line Encyclopedia cell lines, but not in glioblastoma or breast cancer. Activation mutations did not uniformly correlate with proliferation, most cases were pre-metastatic. A gene expression profile was identified, and pathway involvement considered. Significantly, results suggest EGFR over expression and activation are early alterations that likely stall the replication complex through PCNA phosphorylation creating replication stress responsible for DNA damage response and further mutation, but does not promote increased proliferation itself. An argument is presented that the mechanism driving lethality in this tumor cohort could differ from over proliferation seen in other LUAD.

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Section: Discussionmentioning

confidence: 99%

Modulation of proliferation factors in lung adenocarcinoma with an analysis of the transcriptional consequences of genomic EGFR activation

Kucherlapati

2019

Oncotarget

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Immunohistochemical detection of cancer genetic abnormalities

Le,

Oishi,

Mochizuki

et al. 2024

Pathology - Research and Practice

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CRISPR/Cas9 Genome Editing of Epidermal Growth Factor Receptor Sufficiently Abolished Oncogenicity in Anaplastic Thyroid Cancer

et al. 2018

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Anaplastic carcinoma of the thyroid (ATC), also called undifferentiated thyroid cancer, is the least common but most aggressive and deadly thyroid gland malignancy of all thyroid cancers. The aim of this study is to explore essential biomarker and use CRISPR/Cas9 with lentivirus delivery to establish a gene-target therapeutic platform in ATC cells. At the beginning, the gene expression datasets from 1036 cancers from CCLE and 8215 tumors from TCGA were collected and analyzed, showing EGFR is predominantly overexpressed in thyroid cancers than other type of cancers (P = 0.017 in CCLE and P = 0.001 in TCGA). Using CRISPR/Cas9 genomic edit system, ATC cells with EGFR sgRNA lentivirus transfection obtained great disruptions on gene and protein expression, resulting in cell cycle arrest, cell growth inhibition, and most importantly metastasis turn-off ability. In addition, the FDA-approved TKI of afatinib for EGFR targeting also illustrates great anticancer activity on cancer cell death occurrence, cell growth inhibition, and cell cycle arrest in SW579 cells, an EGFR expressing human ATC cell line. Furthermore, off-target effect of using EGFR sgRNAs was measured and found no genomic editing can be detected in off-target candidate gene. To conclude, this study provides potential ATC therapeutic strategies for current and future clinical needs, which may be possible in increasing the survival rate of ATC patients by translational medicine.

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Chromosome 7 Multiplication in EGFR-positive Lung Carcinomas Based on Tissue Microarray Analysis

Abstract: Abstract. Background

Cited by 5 publications

References 40 publications

Modulation of proliferation factors in lung adenocarcinoma with an analysis of the transcriptional consequences of genomic EGFR activation

Modulation of proliferation factors in lung adenocarcinoma with an analysis of the transcriptional consequences of genomic EGFR activation

Immunohistochemical detection of cancer genetic abnormalities

CRISPR/Cas9 Genome Editing of Epidermal Growth Factor Receptor Sufficiently Abolished Oncogenicity in Anaplastic Thyroid Cancer

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