Chromosomal instability analysis and regional tumor heterogeneity in colon cancer

Barresi, Vincenza; Castorina, Sergio; Musso, Nicolò; Capizzi, Carmela; Luca, Tonia; Privitera, Giovanna; Condorelli, D. F.

doi:10.1016/j.cancergen.2016.11.001

Cited by 22 publications

(35 citation statements)

References 41 publications

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“…However, most of the following research has been focused on focal CNAs because of the difficulties to identify driver genes in broader regions 7 , 8 , 33 , 36 , 37 . In the present work we concentrate our attention on broad regions of chromosomal aberration, using a procedure that allows the identification of BCNAs even in the presence of superimposed focal events or artifacts due to cancer heterogeneity 38 . The main hypothesis behind the choice to analyze BCNAs is that the mechanisms providing cancer growth advantage are, at least in part, different between focal and broad chromosomal aberrations 5 .…”

Section: Introductionmentioning

confidence: 99%

Positive Caricature Transcriptomic Effects Associated with Broad Genomic Aberrations in Colorectal Cancer

Condorelli

Spampinato

Valenti

et al. 2018

Sci Rep

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We re-examined the correlation between Broad Genomic Aberrations (BGAs) and transcriptomic profiles in Colorectal Cancer (CRC). Two types of BGAs have been examined: Broad Copy-Number Abnormal regions (BCNAs), distinguished in gain- and loss-type, and Copy-Neutral Loss of Heterozygosities (CNLOHs). Transcripts are classified as “OverT” or “UnderT” if overexpressed or underexpressed comparing CRCs bearing a specific BGA to CRCs not bearing it and as “UpT” or “DownT” if upregulated or downregulated in cancer compared to normal tissue. BGA-associated effects were evaluated by changes in the “Chromosomal Distribution Index” (CDI) of different transcript classes. Data show that UpT are more sensitive than DownT to BCNA-associated gene dosage effects. “Over-UpT” genes are upregulated in cancer and further overexpressed by gene dosage, defining the so called “positive caricature transcriptomic effect”. When Over-UpT genes are ranked according to overexpression, top positions are occupied by genes implicated at the functional and therapeutic level in CRC. We show that cancer-upregulated transcripts are sensitive markers of BCNA-induced effects and suggest that analysis of positive caricature transcriptomic effects can provide clues toward the identification of BCNA-associated cancer driver genes.

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Section: Introductionmentioning

confidence: 99%

Positive Caricature Transcriptomic Effects Associated with Broad Genomic Aberrations in Colorectal Cancer

Condorelli

Spampinato

Valenti

et al. 2018

Sci Rep

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“…14 There are a growing number of studies that report the involvement of ZnTs and ZIPs in a wide variety of cancers. [16][17][18][19] At this time, no study has been undertaken to analyse the global expression of the zinc transporters in colorectal cancer (CRC) and the current study was designed to determine the expression profile of all zinc efflux and influx transporters, respectively SLC30A1 to SLC30A10 and SLC39A1 to SLC39A14 in CRC samples. 15 It is very useful to explore quantitative and qualitative differences characterizing the genetic alterations and biochemical processes in the tumor cells, the application of genome-wide technologies, microarrays, and high throughput sequencing.…”

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confidence: 99%

“…15 It is very useful to explore quantitative and qualitative differences characterizing the genetic alterations and biochemical processes in the tumor cells, the application of genome-wide technologies, microarrays, and high throughput sequencing. [16][17][18][19] At this time, no study has been undertaken to analyse the global expression of the zinc transporters in colorectal cancer (CRC) and the current study was designed to determine the expression profile of all zinc efflux and influx transporters, respectively SLC30A1 to SLC30A10 and SLC39A1 to SLC39A14 in CRC samples.…”

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confidence: 99%

Transcriptome analysis reveals an altered expression profile of zinc transporters in colorectal cancer

Barresi

Valenti

Spampinato

et al. 2018

J of Cellular Biochemistry

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Zinc is a transition metal and catalytic cofactor involved in many biological processes including proliferation, development, differentiation, and metabolism. Zinc transporters (ZnTs) play a fundamental role in cellular zinc homeostasis. ZnTs are responsible of zinc efflux and are encoded by 10 genes belonging to solute carrier family 30A (SLC30A1-10), while zinc-regulated transporter (ZRT)/iron-regulated transporter (IRT)-like protein (ZIP) transporters are responsible for the influx of zinc into the cytoplasm and are encoded by 14 genes belonging to solute carrier family 39A (SLC39A1-14). In this study, we analyzed, by transcriptome analysis, the microRNA levels of ZnT-encoding and ZIP-encoding genes in colorectal cancer (CRC) samples matched to normal colon tissues and in CRC cell lines. Results revealed an upregulation of specific ZnT and ZIP transcripts in CRC. Upregulation of SLC30A5, SLC30A6, SLC30A7 transcripts, encoding zinc efflux transporters ZnT5, ZnT6, ZnT7, localized on endoplasmic reticulum membranes, might be part of a coordinated transcriptional program associated to the increased activity of the early secretory pathway, while transcriptional upregulation of several specific ZIP transporters (SLC39A6, SLC39A7, SLC39A9, SLC39A10, and SLC39A11) could contribute in meeting the increased demand of zinc in cancer cells. Moreover, exon-level analysis of SLC30A9, a nuclear receptor coactivator involved in the transcriptional regulation of Wnt-responsive genes, revealed the differential expression of alternative transcripts in CRC and normal colonic mucosa.

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“…Colorectal cancer has high heterogeneity and many gene mutations. Colorectal cancer can be divided into four molecular types according to different genomes [1][2][3][4][5] . Colorectal cancer involves the accumulation of a series of gene changes, leading to the occurrence of adenoma and adenocarcinoma.…”

Section: Introductionmentioning

confidence: 99%

Clinic-pathological characteristics of MMR protein, KRAS-NRAS-BRAF gene mutation, HER-2 and PD-L1 status in 3822 Chinese colorectal cancer patients

Zhang¹,

Chen²,

Li³

et al. 2020

Preprint

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ObjectivesColorectal cancer is one of the most common cancers. It is a heterogeneous tumor. The aim of this study was to investigate MMR protein expression, KRAS-NRAS-BRAF gene mutation, HER-2 and PD-L1 status in large Chinese CRC patients. MethodsWe reviewed all CRC patients who underwent surgery in Peking University Cancer Hospital between 2010 and 2018 from a prospective collected medical database. We analyzed the clinic-pathological factors associated with immunohistochemistry profiles. We analyzed KRAS-NRAS-BRAF gene changes through ARMS-PCR. ResultsIn our study, d-MMR frequency of CRC was 8%. d-MMR was more common in poorly differentiated colorectal cancer (p = 0.000), and d-MMR was more likely to occur in stage T3 + T4( p = 0.026), and p-MMR was more likely to have lymph node metastasis(p = 0.000). d-MMR was more likely to occur in the right colon, and p-MMR patients usually occur in the rectum sigmoid colon(p = 0.000). p-MMR patients were more likely to have distant metastasis (p = 0.000). We analyzed all 3822 patients with-BRAF status available by IHC, the frequency of BRAF positive expression ration was 1.4%. A total of 1068 colorectal cancer patients had gene analysis by ARMS-PCR. 484 of them had KRAS gene mutation, 28 NRAS gene mutation, 20 BRAF mutation and 536 patients had no mutation. The percentage was 45%, 2.6%, 2%, and 50%, respectively. d-MMR patients usually had BRAF gene mutation (p < 0.001). KRAS and NRAS gene mutations were not associated with MMR status (p = 0.846, p = 0.438). PD-L1 expression was higher in the female group (p = 0.034), poorly differentiated adenocarcinoma group(p = 0.026), and d-MMR group (p = 0.005). The ratio of HER-2 3 + was 1.9%, and HER-2 3 + was usually found in p-MMR group(p = 0.043). ConclusionOur data can improve deeper understanding of colorectal cancer carcinogenic factors and future therapies for colorectal cancer.

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Chromosomal instability analysis and regional tumor heterogeneity in colon cancer

Cited by 22 publications

References 41 publications

Positive Caricature Transcriptomic Effects Associated with Broad Genomic Aberrations in Colorectal Cancer

Positive Caricature Transcriptomic Effects Associated with Broad Genomic Aberrations in Colorectal Cancer

Transcriptome analysis reveals an altered expression profile of zinc transporters in colorectal cancer

Clinic-pathological characteristics of MMR protein, KRAS-NRAS-BRAF gene mutation, HER-2 and PD-L1 status in 3822 Chinese colorectal cancer patients

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