Colorectal carcinoma (CRC) is characterized by wide intratumor heterogeneity with general genomic instability and there is a need for improved diagnostic, prognostic, and therapeutic tools. The liquid biopsy provides a noninvasive route of sample collection for analysis of circulating tumor cells (CTCs) and genomic material, including cell-free DNA (cfDNA), as a complementary biopsy to the solid tumor tissue. The solid biopsy is critical for molecular characterization and diagnosis at the time of collection. The liquid biopsy has the advantage of longitudinal molecular characterization of the disease, which is crucial for precision medicine and patient-oriented treatment. In this review, we provide an overview of CRC and the different methodologies for the detection of CTCs and cfDNA, followed by a discussion on the potential clinical utility of the liquid biopsy in CRC patient care, and lastly, current challenges in the field.

• Klíčová slova
• CRC, CTC, cfDNA, circulating free DNA, circulating tumor DNA, circulating tumor cell, colorectal carcinoma, ctDNA, liquid biopsy, precision medicine,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Colorectal cancer (CRC) is a heterogeneous disease that includes both hereditary and sporadic types of tumors. Tumor initiation and growth is driven by mutational or epigenetic changes that alter the function or expression of multiple genes. The genes predominantly encode components of various intracellular signaling cascades. In this review, we present mouse intestinal cancer models that include alterations in the Wnt, Hippo, p53, epidermal growth factor (EGF), and transforming growth factor β (TGFβ) pathways; models of impaired DNA mismatch repair and chemically induced tumorigenesis are included. Based on their molecular biology characteristics and mutational and epigenetic status, human colorectal carcinomas were divided into four so-called consensus molecular subtype (CMS) groups. It was shown subsequently that the CMS classification system could be applied to various cell lines derived from intestinal tumors and tumor-derived organoids. Although the CMS system facilitates characterization of human CRC, individual mouse models were not assigned to some of the CMS groups. Thus, we also indicate the possible assignment of described animal models to the CMS group. This might be helpful for selection of a suitable mouse strain to study a particular type of CRC.

• Klíčová slova
• carcinoma, consensus molecular subtypes, intestine, oncogenes, signaling cascades, tumor suppressors, tumorigenesis,
• MeSH
• epidermální růstový faktor genetika   MeSH
• geny p53 genetika   MeSH
• karcinogeneze genetika   MeSH
• kolorektální nádory klasifikace   metabolismus   patofyziologie   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• myši MeSH
• nádorová transformace buněk genetika   MeSH
• nádory tračníku genetika   MeSH
• oprava chybného párování bází DNA genetika   MeSH
• protein-serin-threoninkinasy genetika   MeSH
• regulace genové exprese u nádorů genetika   MeSH
• signální dráha Hippo MeSH
• signální dráha Wnt genetika   MeSH
• transformující růstový faktor beta genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• epidermální růstový faktor MeSH
• protein-serin-threoninkinasy MeSH
• transformující růstový faktor beta MeSH

The Czech Republic has one of the highest incidences of colorectal cancer (CRC) in Europe. To evaluate whether sporadic CRCs in Czech patients have specific mutational profiles we analysed somatic genetic changes in known CRC genes (APC, KRAS, TP53, CTNNB1, MUTYH and BRAF, loss of heterozygosity (LOH) at the APC locus, microsatellite instability (MSI), and methylation of the MLH1 promoter) in 103 tumours from 102 individuals. The most frequently mutated gene was APC (68.9% of tumours), followed by KRAS (31.1%), TP53 (27.2%), BRAF (8.7%) and CTNNB1 (1.9%). Heterozygous germline MUTYH mutations in 2 patients were unlikely to contribute to the development of their CRCs. LOH at the APC locus was found in 34.3% of tumours, MSI in 24.3% and MLH1 methylation in 12.7%. Seven tumours (6.9%) were without any changes in the genes tested. The analysis yielded several findings possibly specific for the Czech cohort. Somatic APC mutations did not cluster in the mutation cluster region (MCR). Tumours with MSI but no MLH1 methylation showed earlier onset and more severe mutational profiles compared to MSI tumours with MLH1 methylation. TP53 mutations were predominantly located outside the hot spots, and transitions were underrepresented. Our analysis supports the observation that germline MUTYH mutations are rare in Czech individuals with sporadic CRCs. Our findings suggest the influence of specific ethnic genetic factors and/or lifestyle and dietary habits typical for the Czech population on the development of these cancers.

• MeSH
• adaptorové proteiny signální transdukční genetika   MeSH
• běloši genetika   MeSH
• beta-katenin genetika   MeSH
• DNA-glykosylasy genetika   MeSH
• dospělí MeSH
• jaderné proteiny genetika   MeSH
• kolorektální nádory genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metylace DNA genetika   MeSH
• mikrosatelitní nestabilita MeSH
• mladiství MeSH
• mladý dospělý MeSH
• MutL homolog 1 MeSH
• nádorový supresorový protein p53 genetika   MeSH
• promotorové oblasti (genetika) genetika   MeSH
• protein familiární adenomatózní polypózy genetika   MeSH
• protoonkogenní proteiny B-Raf genetika   MeSH
• protoonkogenní proteiny p21(ras) MeSH
• protoonkogenní proteiny genetika   MeSH
• Ras proteiny genetika   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• zárodečné mutace genetika   MeSH
• ztráta heterozygozity genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• adaptorové proteiny signální transdukční MeSH
• APC protein, human MeSH Prohlížeč
• beta-katenin MeSH
• BRAF protein, human MeSH Prohlížeč
• CTNNB1 protein, human MeSH Prohlížeč
• DNA-glykosylasy MeSH
• jaderné proteiny MeSH
• KRAS protein, human MeSH Prohlížeč
• MLH1 protein, human MeSH Prohlížeč
• MutL homolog 1 MeSH
• mutY adenine glycosylase MeSH Prohlížeč
• nádorový supresorový protein p53 MeSH
• protein familiární adenomatózní polypózy MeSH
• protoonkogenní proteiny B-Raf MeSH
• protoonkogenní proteiny p21(ras) MeSH
• protoonkogenní proteiny MeSH
• Ras proteiny MeSH

AIM: To evaluate the frequency of the loss of the Adenomatous Polyposis Coli (APC) protein and to compare the APC status with the characteristics of colorectal adenomas. METHODS: Immunohistochemical analysis of the APC protein was performed on 118 adenomas and the results were compared with parameters of malignant potential, location of adenomas, macroscopic appearance and age of the patients. RESULTS: A complete loss of the APC protein was found in 28 (24%) adenomas, while 90 (76%) were APC positive. The mean size of adenomas was 13.5 +/- 14.2 mm (95% CI 10.5-16.5) in APC-positive, and 13.8 +/- 15.5 mm (95% CI 7.8-19.8) in APC-negative adenomas (P = 0.364). Statistical analysis revealed no difference between APC-positive and negative adenomas as to the histological type (P = 0.327) and grade of dysplasia (P = 0.494). We found that even advanced adenomas did not differ in their APC status from the non-advanced tumors (P = 0.414). Finally, no difference was found when the location (P = 0.157), macroscopic appearance (P = 0.571) and age of patients (P = 0.438) were analysed and compared between both APC positive and negative adenomas. CONCLUSION: Most adenomas expressed full-length APC protein, suggesting that protein expression is not a reliable marker for assessment of APC gene mutation. Complete loss of APC protein did not influence morphology, location, or appearance of adenomas, nor was it affected by the patient's age.

• MeSH
• adenom chemie   genetika   patologie   MeSH
• dospělí MeSH
• fenotyp MeSH
• imunohistochemie MeSH
• kolorektální nádory chemie   genetika   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace MeSH
• mutační analýza DNA MeSH
• nádorové biomarkery analýza   MeSH
• protein familiární adenomatózní polypózy analýza   genetika   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• stanovení celkové genové exprese MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• nádorové biomarkery MeSH
• protein familiární adenomatózní polypózy MeSH