Gain-Type Aneuploidies Influence the Burden of Selective Long Non-Coding Transcripts in Colorectal Cancer.

Chromosomal instability is a hallmark of colorectal carcinogenesis and produces an accumulation of different forms of aneuploidies or broad copy number aberrations. Colorectal cancer is characterized by gain-type broad copy number aberrations, specifically in Chr20, Chr8q, Chr13 and Chr7, but their roles and mechanisms in cancer progression are not fully understood. It has been suggested that broad copy number gains might contribute to tumor development through the so-called caricature transcriptomic effect. We intend to investigate the impact of broad copy number gains on long non-coding RNAs' expression in colorectal cancer, given their well-known role in oncogenesis. The influence of such chromosomal aberrations on lncRNAs' transcriptome profile was investigated by SNP and transcriptome arrays in our series of colorectal cancer samples and cell lines. The correlation between aneuploidies and transcriptomic profiles led us to obtain a class of Over-UpT lncRNAs, which are transcripts upregulated in CRC and further overexpressed in colon tumors bearing specific chromosomal aberrations. The identified lncRNAs can contribute to a wide interaction network to establish the cancer driving effect of gain-type aneuploidies.

Transcript-Targeted Therapy Based on RNA Interference and Antisense Oligonucleotides: Current Applications and Novel Molecular Targets.

The development of novel target therapies based on the use of RNA interference (RNAi) and antisense oligonucleotides (ASOs) is growing in an exponential way, challenging the chance for the treatment of the genetic diseases and cancer by hitting selectively targeted RNA in a sequence-dependent manner. Multiple opportunities are taking shape, able to remove defective protein by silencing RNA (e.g., Inclisiran targets mRNA of protein PCSK9, permitting a longer half-life of LDL receptors in heterozygous familial hypercholesteremia), by arresting mRNA translation (i.e., Fomivirsen that binds to UL123-RNA and blocks the translation into IE2 protein in CMV-retinitis), or by reactivating modified functional protein (e.g., Eteplirsen able to restore a functional shorter dystrophin by skipping the exon 51 in Duchenne muscular dystrophy) or a not very functional protein. In this last case, the use of ASOs permits modifying the expression of specific proteins by modulating splicing of specific pre-RNAs (e.g., Nusinersen acts on the splicing of exon 7 in SMN2 mRNA normally not expressed; it is used for spinal muscular atrophy) or by downregulation of transcript levels (e.g., Inotersen acts on the transthryretin mRNA to reduce its expression; it is prescribed for the treatment of hereditary transthyretin amyloidosis) in order to restore the biochemical/physiological condition and ameliorate quality of life. In the era of precision medicine, recently, an experimental splice-modulating antisense oligonucleotide, Milasen, was designed and used to treat an 8-year-old girl affected by a rare, fatal, progressive form of neurodegenerative disease leading to death during adolescence. In this review, we summarize the main transcriptional therapeutic drugs approved to date for the treatment of genetic diseases by principal regulatory government agencies and recent clinical trials aimed at the treatment of cancer. Their mechanism of action, chemical structure, administration, and biomedical performance are predominantly discussed.

Downregulation of the Astroglial Connexin Expression and Neurodegeneration after Pilocarpine-Induced Status Epilepticus.

Astrocytic networks and gap junctional communication mediated by connexins (Cxs) have been repeatedly implicated in seizures, epileptogenesis, and epilepsy. However, the effect of seizures on Cx expression is controversial. The present study focused on the response of Cxs to status epilepticus (SE), which is in turn an epileptogenic insult. The expression of neuronal Cx36 and astrocytic Cx30 and Cx43 mRNAs was investigated in the brain of rats in the first day after pilocarpine-induced SE. In situ hybridization revealed a progressive decrease in Cx43 and Cx30 mRNA levels, significantly marked 24 h after SE onset in neocortical areas and the hippocampus, and in most thalamic domains, whereas Cx36 mRNA did not exhibit obvious changes. Regional evaluation with quantitative real-time-RT-PCR confirmed Cx43 and Cx30 mRNA downregulation 24 h after SE, when ongoing neuronal cell death was found in the same brain regions. Immunolabeling showed at the same time point marked a decrease in Cx43, microglia activation, and interleukin-1ß induction in some microglial cells. The data showed a transient downregulation of astroglial Cxs in the cortical and thalamic areas in which SE triggers neurodegenerative events in concomitance with microglia activation and cytokine expression. This could potentially represent a protective response of neuroglial networks to SE-induced acute damage.

Gastric ghrelin cells in obese patients are hyperactive.

BACKGROUND/OBJECTIVES: Distribution and activity of ghrelin cells in the stomach of obese subjects are controversial. SUBJECTS/METHODS: We examined samples from stomachs removed by sleeve gastrectomy in 49 obese subjects (normoglycemic, hyperglycemic and diabetic) and quantified the density of ghrelin/chromogranin endocrine cells by immunohistochemistry. Data were compared with those from 13 lean subjects evaluated by gastroscopy. In 44 cases (11 controls and 33 obese patients) a gene expression analysis of ghrelin and its activating enzyme ghrelin O-acyl transferase (GOAT) was performed. In 21 cases (4 controls and 17 obese patients) the protein levels of unacylated and acylated-ghrelin were measured by ELISA tests. In 18 cases (4 controls and 14 obese patients) the morphology of ghrelin-producing cells was evaluated by electron microscopy. RESULTS: The obese group, either considered as total population or divided into subgroups, did not show any significant difference in ghrelin cell density when compared with control subjects. Inter-glandular smooth muscle fibres were increased in obese patients. In line with a positive trend of the desacylated form found by ELISA, Ghrelin and GOAT mRNA expression in obese patients was significantly increased. The unique ghrelin cell ultrastructure was maintained in all obese groups. In the hyperglycemic obese patients, the higher ghrelin expression matched with ultrastructural signs of endocrine hyperactivity, including expanded rough endoplasmic reticulum and reduced density, size and electron-density of endocrine granules. A positive correlation between ghrelin gene expression and glycemic values, body mass index and GOAT was also found. All obese patients with type 2 diabetes recovered from diabetes at follow-up after 5 months with a 16.5% of weight loss. CONCLUSIONS: Given the known inhibitory role on insulin secretion of ghrelin, these results suggest a possible role for gastric ghrelin overproduction in the complex architecture that takes part in the pathogenesis of type 2 diabetes.

Synthesis of Bisphenol Neolignans Inspired by Honokiol as Antiproliferative Agents.

Honokiol (2) is a natural bisphenol neolignan showing a variety of biological properties, including antitumor activity. Some studies pointed out 2 as a potential anticancer agent in view of its antiproliferative and pro-apoptotic activity towards tumor cells. As a further contribution to these studies, we report here the synthesis of a small library of bisphenol neolignans inspired by honokiol and the evaluation of their antiproliferative activity. The natural lead was hence subjected to simple chemical modifications to obtain the derivatives 3-9; further neolignans (12a-c, 13a-c, 14a-c, and 15a) were synthesized employing the Suzuki-Miyaura reaction, thus obtaining bisphenols with a substitution pattern different from honokiol. These compounds and the natural lead were subjected to antiproliferative assay towards HCT-116, HT-29, and PC3 tumor cell lines. Six of the neolignans show GI50 values lower than those of 2 towards all cell lines. Compounds 14a, 14c, and 15a are the most effective antiproliferative agents, with GI50 in the range of 3.6-19.1 µM, in some cases it is lower than those of the anticancer drug 5-fluorouracil. Flow cytometry experiments performed on these neolignans showed that the inhibition of proliferation is mainly due to an apoptotic process. These results indicate that the structural modification of honokiol may open the way to obtaining antitumor neolignans more potent than the natural lead.

Chromosomal Density of Cancer Up-Regulated Genes, Aberrant Enhancer Activity and Cancer Fitness Genes Are Associated with Transcriptional Cis-Effects of Broad Copy Number Gains in Colorectal Cancer.

Broad Copy Number Gains (BCNGs) are copy-number increases of chromosomes or large segments of chromosomal arms. Publicly-available single-nucleotide polymorphism (SNP) array and RNA-Seq data of colon adenocarcinoma (COAD) samples from The Cancer Genome Atlas (TCGA) consortium allowed us to design better control groups in order to identify changes in expression due to highly recurrent BCNGs (in chromosomes 20, 8, 7, 13). We identified: (1) Overexpressed Transcripts (OverT), transcripts whose expression increases in "COAD groups bearing a specific BCNG" in comparison to "control COAD groups" not bearing it, and (2) up-regulated/down-regulated transcripts, transcripts whose expression increases/decreases in COAD groups in comparison to normal colon tissue. An analysis of gene expression reveals a correlation between the density of up-regulated genes per selected chromosome and the recurrence rate of their BCNGs. We report an enrichment of gained enhancer activity and of cancer fitness genes among OverT genes. These results support the hypothesis that the chromosomal density of overexpressed cancer fitness genes might play a significant role in the selection of gained chromosomes during cancer evolution. Analysis of functional pathways associated with OverT suggest that some multi-subunit protein complexes (eIF2, eIF3, CSTF and CPSF) are candidate targets for silencing transcriptional therapy.

Fusion Transcripts of Adjacent Genes: New Insights into the World of Human Complex Transcripts in Cancer.

The awareness of genome complexity brought a radical approach to the study of transcriptome, opening eyes to single RNAs generated from two or more adjacent genes according to the present consensus. This kind of transcript was thought to originate only from chromosomal rearrangements, but the discovery of readthrough transcription opens the doors to a new world of fusion RNAs. In the last years many possible intergenic cis-splicing mechanisms have been proposed, unveiling the origins of transcripts that contain some exons of both the upstream and downstream genes. In some cases, alternative mechanisms, such as trans-splicing and transcriptional slippage, have been proposed. Five databases, containing validated and predicted Fusion Transcripts of Adjacent Genes (FuTAGs), are available for the scientific community. A comparative analysis revealed that two of them contain the majority of the results. A complete analysis of the more widely characterized FuTAGs is provided in this review, including their expression pattern in normal tissues and in cancer. Gene structure, intergenic splicing patterns and exon junction sequences have been determined and here reported for well-characterized FuTAGs. The available functional data and the possible roles in cancer progression are discussed.

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

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.

Modulation of the TGF-ß1-induced epithelial to mesenchymal transition (EMT) mediated by P1 and P2 purine receptors in MDCK cells.

Epithelial to mesenchymal transition (EMT) occurs during embryogenesis or under pathological conditions such as hypoxia, injury, chronic inflammation, or tissue fibrosis. In renal tubular epithelial cells (MDCK), TGF-ß1 induces EMT by reducing or increasing epithelial or mesenchymal marker expression, respectively. In this study, we confirmed that the cAMP analogues, 8-CPT-cAMP or N6-Ph-cAMP, inhibited the TGF-ß1-driven overexpression of the mesenchymal markers ZEB-1, Slug, Fibronectin, and α-SMA. Furthermore, we showed that A1, A2A, P2Y1, P2Y11, and P2X7 purine receptor agonists modulated the TGF-ß1-induced EMT through the involvement of PKA and/or MAPK/ERK signaling. The stimulation of A2A receptor reduced the overexpression of the EMT-related markers, mainly through the cAMP-dependent PKA pathway, as confirmed by cell pre-treatment with Myr-PKI. Both A1 and P2Y1 receptor stimulation exacerbated the TGF-ß1-driven effects, which were reduced by cell pre-treatment with the MAPK inhibitor PD98059, according to the increased ERK1/2 phosphorylation upon receptor activation. The effects induced by P2Y11 receptor activation were oppositely modulated by PKA or MAPK inhibition, in line with the dual nature of the Gs- and Gq-coupled receptor. Differently, P2X7 receptor induced, per se, similar and not additive effects compared to TGF-ß1, after prolonged cell exposure to BzATP. These results suggest a putative role of purine receptors as target for anti-fibrotic agents.

Dihydrobenzofuran Neolignanamides: Laccase-Mediated Biomimetic Synthesis and Antiproliferative Activity.

The biomimetic synthesis of a small library of dihydrobenzofuran neolignanamides (the natural trans-grossamide (4) and the related compounds 21-28) has been carried out through an eco-friendly oxidative coupling reaction mediated by Trametes versicolor laccase. These products, after complete spectroscopic characterization, were evaluated for their antiproliferative activity against Caco-2 (colon carcinoma), MCF-7 (mammary adenocarcinoma), and PC-3 (prostate cancer) human cells, using an MTT bioassay. The racemic neolignamides (±)-21 and (±)-27, in being the most lipophilic in the series, were potently active, with GI50 values comparable to or even lower than that of the positive control 5-FU. The racemates were resolved through chiral HPLC, and the pure enantiomers were subjected to ECD measurements to establish their absolute configurations at C-2 and C-3. All enantiomers showed potent antiproliferative activity, with, in particular, a GI50 value of 1.1 µM obtained for (2R,3R)-21. The effect of (±)-21 on the Caco-2 cell cycle was evaluated by flow cytometry, and it was demonstrated that (±)-21 exerts its antiproliferative activity by inducing cell cycle arrest and apoptosis.

ICAM-1 and SRD5A1 gene polymorphisms in symptomatic peripheral artery disease.

The genotype distribution of two gene polymorphisms, previously associated with peripheral artery disease (PAD), has been evaluated in a population of diabetic (DPAD) and non-diabetic (NDPAD) patients affected by symptomatic PAD (stages II-IV). A decreased frequency of the AA genotype of rs5498 (ICAM-1) was observed in the PAD subjects compared to controls but this result did not reach statistical significance (p=0.06 by chi-squared test). On the contrary, a significant increase in the frequency of the GG homozygous genotype of rs248793 (SRD5A1) was observed in the PAD patient group in comparison to controls (p=0.01). These data confirm that the GG genotype of rs248793 in the SRD5A1 gene is significantly associated with symptomatic PAD and show a trend towards a stronger association with the non-diabetic status.

Genome-wide analysis of recurrent copy-number alterations and copy-neutral loss of heterozygosity in head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the eighth most commonly diagnosed malignancy worldwide, and it is generally characterized by a poor prognosis. The aim of our study has been to identify possible recurring genomic abnormalities in this malignancy, likely to have a key role in pathogenesis. METHODS: The single-nucleotide polymorphism (SNP)-array data relative to 19 HNSCC samples (submitted by Poage et al., PloS ONE 2010; 5: e9651), accessible at NCBI GEO database (GSE20939), were analyzed using criteria that take into account both genotyping and intensity data. By this method, we determined the number and localization of recurrent copy-neutral loss of heterozygosity (CN-LOH) regions and compared them with recurrent somatic copy-number alterations (CNAs). RESULTS: Single-nucleotide polymorphism-array data analysis allowed us to detect, for the first time in HNSCC, chromosomal segment of CN-LOHs in addition to CNAs. Chromosomal alterations have been detected in 14 (73.7%) of 19 samples, and the 12.1% of all alterations observed (LOHs, gains, and CN-LOHs) were CN-LOHs. The most recurrent gain events, occurring in 78.5% of cases (11 samples), were harbored within 8q21.11-q21.13 and 8q23.1-q24.22 loci, while the most recurrent loss and CN-LOH events were present at 3p21.31-p21.1 (57.1%; 8 samples) and 17p13.3-p13.1 (28.6%; 4 samples) loci, respectively. CONCLUSION: The investigated chromosomal regions, in particular those with CN-LOH, harbored some interesting genes, such as HIC1, DOCK8, KANK1, and NOTCH1 whose role, mutations and epigenetic modifications in HNSCC deserve to be investigated, in order to understand the significance of CN-LOH events in HNSCC pathogenesis.

Measuring cancer driving force of chromosomal aberrations through multi-layer Boolean implication networks.

Multi-layer Complex networks are commonly used for modeling and analysing biological entities. This paper presents the advantage of using COMBO (Combining Multi Bio Omics) to suggest a new role of the chromosomal aberration as a cancer driver factor. Exploiting the heterogeneous multi-layer networks, COMBO integrates gene expression and DNA-methylation data in order to identify complex bilateral relationships between transcriptome and epigenome. We evaluated the multi-layer networks generated by COMBO on different TCGA cancer datasets (COAD, BLCA, BRCA, CESC, STAD) focusing on the effect of a specific chromosomal numerical aberration, broad gain in chromosome 20, on different cancer histotypes. In addition, the effect of chromosome 8q amplification was tested in the same TCGA cancer dataset. The results demonstrate the ability of COMBO to identify the chromosome 20 amplification cancer driver force in the different TCGA Pan Cancer project datasets.

Temporary serine protease inhibition and the role of SPINK2 in human bone marrow.

Protease temporary inhibitors are true substrates that bind the catalytic site with high affinity but are slowly degraded, thus acting as inhibitor for a defined time window. Serine peptidase inhibitor Kazal type (SPINK) family is endowed with such functional property whose physiological meaning is poorly explored. High expression of SPINK2 in some hematopoietic malignancies prompted us to investigate its role in adult human bone marrow. We report here the physiological expression of SPINK2 in hematopoietic stem and progenitor cells (HSPCs) and mobilized cluster differentiation 34 (CD34)+ cells. We determined the SPINK2 degradation constant and derived a mathematical relationship predicting the zone of inhibited target protease activity surrounding the SPINK2-secreting HSPCs. Analysis of putative target proteases for SPINK2 revealed the expression of PRSS2 and PRSS57 in HSPCs. Our combined results suggest that SPINK2 and its target serine proteases might play a role in the intercellular communication within the hematopoietic stem cell niche.

Aberrations of Chromosomes 1 and 16 in Breast Cancer: A Framework for Cooperation of Transcriptionally Dysregulated Genes.

Derivative chromosome der(1;16), isochromosome 1q, and deleted 16q-producing arm-level 1q-gain and/or 16q-loss-are recurrent cytogenetic abnormalities in breast cancer, but their exact role in determining the malignant phenotype is still largely unknown. We exploited The Cancer Genome Atlas (TCGA) data to generate and analyze groups of breast invasive carcinomas, called 1,16-chromogroups, that are characterized by a pattern of arm-level somatic copy number aberrations congruent with known cytogenetic aberrations of chromosome 1 and 16. Substantial differences were found among 1,16-chromogroups in terms of other chromosomal aberrations, aneuploidy scores, transcriptomic data, single-point mutations, histotypes, and molecular subtypes. Breast cancers with a co-occurrence of 1q-gain and 16q-loss can be distinguished in a "low aneuploidy score" group, congruent to der(1;16), and a "high aneuploidy score" group, congruent to the co-occurrence of isochromosome 1q and deleted 16q. Another three groups are formed by cancers showing separately 1q-gain or 16q-loss or no aberrations of 1q and 16q. Transcriptome comparisons among the 1,16-chromogroups, integrated with functional pathway analysis, suggested the cooperation of overexpressed 1q genes and underexpressed 16q genes in the genesis of both ductal and lobular carcinomas, thus highlighting the putative role of genes encoding gamma-secretase subunits (APH1A, PSEN2, and NCSTN) and Wnt enhanceosome components (BCL9 and PYGO2) in 1q, and the glycoprotein E-cadherin (CDH1), the E3 ubiquitin-protein ligase WWP2, the deubiquitinating enzyme CYLD, and the transcription factor CBFB in 16q. The analysis of 1,16-chromogroups is a strategy with far-reaching implications for the selection of cancer cell models and novel experimental therapies.

Antiproliferative effects induced by guanine-based purines require hypoxanthine-guanine phosphoribosyltransferase activity.

Guanine (GUA), guanosine and GMP exert a marked growth inhibition on the U87 glioma cell line that is not seen with other tested nucleotides, nucleosides and nucleobases. This effect could be replicated in several different human tumoral cell lines. Guanine shows a higher potency than guanosine or GMP, and co-treatments with adenosine or adenine are able to antagonize or revert the antiproliferative effect of guanine. The loss of the guanine effect in a cell line bearing a mutated inactive hypoxanthine-guanine phosphoribosyltransferase (HGPRT), and the decreased potency of GUA in U87 cells silenced for HGPRT transcripts, demonstrates the central role of the intracellular metabolism of GUA for growth-inhibitory effects. Considering the potential application of growth-inhibitory substances in anticancer therapy, knowledge of the molecular mechanism underlying GUA-induced effects encourages studies aimed at defining possible tumoral targets for experimental therapies.

Dectin-1 and TIM3 Expression in Deep Vein Thrombosis of Lower Limbs (DVTLL).

The pathophysiological mechanisms of venous thromboembolism are venous stasis, endothelial damage, and hypercoagulability, while less attention has been given to the role of both innate and native immunity. In this paper, we investigate the involvement of the activated immune system detected through some indicators such as TIM3 and Dectin-1 expressed by T lymphocytes. TIM3 and Dectin-1, two surface molecules that regulate the fine-tuning of innate and adaptive immune responses, were evaluated in patients affected by deep vein thrombosis of lower limbs (DVTLL). CD3+, CD4+ and CD8+ T lymphocytes obtained from patients affected by DVTLL were analysed using fluorescence-conjugated antibodies for TIM3 and Dectin-1 by an imaging flow cytometer. DVTLL patients showed a higher number of CD4+ and CD8+ T lymphocytes. TIM3 expression in T lymphocytes was very low in both DVTLL patients and controls. On the contrary, an increase in Dectin-1+ cells among CD4+ and CD8+ T lymphocytes from DVTLL patients was observed. Dectin-1 is known to play a role in inflammation and immunity and our result suggests its potential involvement in thrombotic venous disease.

The Current Practice of Lynch Syndrome Diagnosis and Management in Italy: A Qualitative Assessment.

BACKGROUND: Lynch syndrome (LS) is the most frequent form of hereditary colorectal cancer (CRC; up to 3-5% of the total CRC burden) and predisposes to the development of other cancers. Multidisciplinary diagnostic strategies are relevant both to the index cases and to their at-risk relatives, but their implementation is still limited. Our study aimed to explore LS testing practices in Italy. METHODS: In order to ascertain the current practice of LS diagnosis and management, we conducted a qualitative assessment by sending a questionnaire to health care professionals at 4 Italian hospitals selected as "models" representing different hospital settings. Based on the surveys, we reconstructed the management pathways for CRC patients in terms of diagnostic strategies and health professionals involved. RESULTS: Seven of the 8 invited professionals filled in the questionnaire. Noncompliance with the latest guidelines was reported, as no tumor "screening" was performed on CRC cases. The lack of a structured multidisciplinary team who manages CRC patients from risk assessment to diagnosis and follow-up was reported. The availability of professionals and laboratory technologies differ widely between hospitals. As for cascade testing of at-risk relatives, a systematic and active approach was absent in all the considered hospitals. CONCLUSIONS: Our study shows that no structured and standardized pathways for the diagnosis and management of LS patients are currently in place in Italy. We envisage that by extending our research to further experiences and countries, an increasing awareness of the topic can be translated into a health gain for hereditary CRC patients and their at-risk relatives.

Chromosomal instability analysis and regional tumor heterogeneity in colon cancer.

Chromosomal instability (CIN) is classically defined as an increase in the rate at which numerical or structural chromosomal aberrations are acquired in a cancer cell. The number of somatic copy number abnormalities (CNAs) revealed by high resolution genomic array can be considered as a surrogate marker for CIN, but several points, related to sample processing and data analysis, need to be standardized. In this work we analyzed 51 CRC samples and matched normal mucosae by whole genome SNP arrays and compared different bioinformatics tools in order to identify broad (>25% of a chromosomal arm) and focal somatic copy number abnormalities (BCNAs and FCNAs respectively). In 15 tumors, two samples, separated by at least 1 cm, were taken from the same tumor mass (double-sampling pairs) in order to evaluate differences in detection of chromosomal abnormalities between distant regions of the same tumor and their influence on CIN quantitative and qualitative analysis. Our data show a high degree of correlation of the quantitative CIN index (somatic BCNA number) between distant tumor regions. On the contrary, a lower correlation is observed in terms of chromosomal distribution of BCNAs, as summarized by a simplified cytogenetic table. Quantitative or qualitative analysis of FCNAs, including homozygous deletions and high level amplifications, did not add further information on the CIN status. The use of the index "somatic BCNA number" can be proposed for a robust classification of tumors as CIN positive or negative even in the presence of a significant tumor regional heterogeneity.