BACKGROUND: Single nucleotide polymorphisms can create a genetic microenvironment in some tumors that affects the course of treatment, resistance, etc. Whether single nucleotide polymorphisms have an impact on gastrointestinal stromal tumor (GIST) development and disease progression is not yet accurately verified. KIT SNPM541L in exon 10 correlates with a worse prognosis of many cancers. The impact of KIT SNPM541L in GISTs is relatively unknown and, therefore, its analyses could have potential in patient therapy and could provide more detailed information on tumor character, clinical presentation, or tumor behavior in treatment. AIM: The aim of the study was the analysis of the biological and clinical significance of the KIT SNPM541L polymorphism in exon 10. MATERIALS AND METHODS: Paraffin sample tissues were obtained from the National GIST Register in Martin. Retrospective samples from 177 GIST patients were divided into several groups. Detection of SNPM541L was performed by Sanger sequencing. Statisitical analyses were performed to determine the prevalence of KIT SNPM541L in the Slovak GIST cohort, to search for correlation between c-KIT status and clinicopathological, molecular and biological data. RESULTS: Overall, 29 samples out of 177 showed KIT SNPM541L polymorphism. CONCLUSION: Our results do not support the association between KIT SNPM541L and increased risk of relapse in localized primary GISTs. Additionally, we found a positive correlation between KIT SNPM541L occurrence and earlier onset of relapse in PDGFRa and WT subgroup of GISTs.
- MeSH
- dospělí MeSH
- gastrointestinální nádory epidemiologie genetika patologie MeSH
- gastrointestinální stromální tumory epidemiologie genetika patologie MeSH
- jednonukleotidový polymorfismus * MeSH
- lidé středního věku MeSH
- lidé MeSH
- míra přežití MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nádorové biomarkery genetika MeSH
- následné studie MeSH
- prognóza MeSH
- protoonkogenní proteiny c-kit genetika MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři 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
- Geografické názvy
- Evropa MeSH
Východiská: Podstatou moderných postupov liečby onkologických pacientov je v dnešnej dobe zacielenie konkrétnych molekúl zapojených do bunkovej signalizácie asociovanej s nádorovou iniciáciou a progresiou. Úspech uvedeného prístupu závisí od správne zvoleného diagnostického testu s vysokou citlivosťou, ktorý identifikuje výskyt a hladinu vybraných biomarkerov u pacientov pre selekciu tých, ktorí budú na liečivo reagovať a budú z neho benefitovať. Vývoj nových technológií a modernizácia tých známych, prispievajú k inováciám molekulárnej charakterizácie karcinómov, ktorá umožňuje detekciu mutačného stavu pacienta s vysokou citlivosťou a špecifickosťou. Cieľ: V práci diskutujeme o využití polymerázovej reťazovej reakcie (PCR) tretej generácie, tzv. droplet digitálnej PCR (ddPCR), v molekulárnej diagnostike karcinómov. Podľa štúdií uvedených v našom prehľade predstavuje ddPCR sľubný nástroj pri vytváraní genetického profilu pacientov s onkologickým ochorením. Optimalizácia a presná validácia môžu preto umožniť postupnú implementáciu ddPCR do klinickej praxe v oblasti onkológie.
Background: Nowadays, modern treatment methods for cancer patients are based on targeting specific molecules involved in cellular signaling system associated with tumor initiation and progression. The success of such approach depends on a correctly chosen diagnostic test with high sensitivity that identifies the occurrence and level of biomarkers in patients to select those who will respond and benefit from the treatment. The development of new technologies and the upgrades of the known ones contribute to the innovations in molecular characterization of cancer, which allows the detection of patient’s mutational status with high sensitivity and specificity. Purpose: Here, we discuss the utilization of the third-generation type of polymerase chain reaction (PCR), droplet digital PCR (ddPCR), in the molecular diagnostics of oncology diseases. According to the studies reported in our review, ddPCR represents a promising tool in genetic profiling of cancer patients. Therefore, the optimization and precise validation may enable gradual implementation of ddPCR into clinical practice in the field of oncology.
The colorectal cancer harbor germline, somatic or epimutations in mismatch repair genes, MUTYH or POLE gene, which lead to the hypermutated and ultramutator phenotypes with increased immune response. The mutations in POLE gene were reported to occur more frequently in early-onset colorectal cancer (EOCRC), and the patients are strong candidates for checkpoint inhibitor therapy. Here, we report mutation analysis within the endonuclease domain of the POLE gene in the cohort of patients with EOCRC in order to identify recurrent or new mutations and evaluate their association with the presence of tumor-infiltrating lymphocytes (TILs) and peritumoral lymphoid reaction. We have shown a significant association between MSI tumors and TILs (p = 0.004). Using sensitive single-tube nested PCR with subsequent Sanger sequencing, we have found in one female patient diagnosed at age 48 with rectal adenocarcinoma with mucinous elements staged pT3pN2pM1 a silent variant within the exon 9 NM_006231.3 c.849 C > T, NP_00622.2 p.Leu283 = recorded in dSNP as rs1232888774 with MAF = 0.00002. In silico prediction, result showed possible involvement into splicing; therefore, this rare variant can be involved into EOCRC pathogenesis. In the time of precise medicine, it is important to develop screening strategies also for less common conditions such as EOCRC allowing to predict tailored therapy for younger patients suffering from CRC that harbor mutations in the POLE gene.
- MeSH
- DNA-polymerasa II genetika MeSH
- dospělí MeSH
- genotypizační techniky MeSH
- kolorektální nádory genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- mutace * MeSH
- proteiny vázající poly-ADP-ribosu genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE: Cancer is a serious health issue and a leading cause of death worldwide. Most of the cancer patients (approximately 90%) do not die from the consequences of the primary tumor development, but due to a heavily treatable metastatic invasion. During the lengthy multistep process of carcinogenesis, there are a lot of opportunities available to reverse or slow down the tissue invasion or the process of tumor metastasis formation. RESULTS: Current research has brought many promising results from anti-metastatic experimental studies, and has shown that chemoprevention by natural or semisynthetic phytochemicals with plethora of biological activities could be one of the potentially effective options in the fight against this problem. However, there is a lack of clinical trials to confirm these findings. In this review, we focused on summarization and discussion of the general features of metastatic cancer, and recent preclinical and clinical studies dealing with anti-metastatic potential of various plant-derived compounds. CONCLUSIONS: Based on our findings, we can conclude and confirm our hypothesis that phytochemicals with pleiotropic anticancer effects can be very useful in retarding and/or reversing the metastasis process, and can also be used to prevent tissue invasion and metastases. But, further studies in this area are certainly necessary and desirable.
- MeSH
- biologické markery MeSH
- chemoprofylaxe MeSH
- chemorezistence účinky léků MeSH
- epitelo-mezenchymální tranzice účinky léků MeSH
- fytogenní protinádorové látky chemie farmakologie terapeutické užití MeSH
- fytonutrienty chemie farmakologie terapeutické užití MeSH
- invazivní růst nádoru MeSH
- klinická studie jako téma MeSH
- lidé MeSH
- metastázy nádorů MeSH
- nádorové mikroprostředí MeSH
- nádory etiologie metabolismus patologie terapie MeSH
- preklinické hodnocení léčiv MeSH
- protokoly protinádorové kombinované chemoterapie škodlivé účinky terapeutické užití MeSH
- regulace genové exprese u nádorů MeSH
- signální transdukce účinky léků MeSH
- staging nádorů MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
