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
BACKGROUND: Retinopathy of prematurity (ROP) is a multifactorial disease occurring in preterm neonates, caused by incorrect development of retinal blood vessels. It has been suggested that, in addition to gestational age, weight, and oxygen supplementation, genetic factors can play a role in the pathogenesis of ROP. METHODS: In the present prospective study, 97 neonates were enrolled based on the gestational age and weight, and genomic DNA from patients diagnosed with ROP and premature newborns without ROP was collected. The DNA sequence of protein coding and 5 ́and 3 ́ untranslated regions (UTRs) of the frizzled-4 (FZD4) gene and the genotype of the locus rs7934165:G˃A (NM_170731.4: c.3 + 10976 C˃T) within the brain-derived neurotrophic factor gene (BDNF) were determined. RESULTS: We detected a significant association between rs61749246:C˃A (NM_012193.3: c.*2G˃T) and ROP in a general genetic model as well as in a multiplicative model and by the Cochran-Armitage test for trend. Moreover, rs61749246 was strongly associated with ROP, requiring surgical intervention. CONCLUSION: We suggest that rs61749246:C˃A of the FZD4 gene is likely associated with the development of ROP. It is necessary to confirm this suggestion in larger studies.
- MeSH
- dospělí MeSH
- frizzled receptory genetika MeSH
- genotyp MeSH
- gestační stáří MeSH
- jednonukleotidový polymorfismus * MeSH
- lidé MeSH
- mozkový neurotrofický faktor genetika MeSH
- prospektivní studie MeSH
- retinopatie nedonošených genetika patologie MeSH
- rizikové faktory MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
