Objective To detective KRAS and BRAF mutations in gastrointestinal stromal tumors (GISTs) and explore its significance in resistance of imatinib treatment. Methods Three hundred and eighty-one c-kit/PDGFRA mutation samples, 119 c-kit/PDGFRA wild type samples, and 19 pairs of samples before and after imatinib resistance from 519 patients with GIST were enrolled in this study. Polymerase chain reaction was used to detect KRAS exon 2 and BRAF exon 15 mutations. The survival data were evaluated in patients with KRAS or BRAF mutation. Results KRAS mutation was found in 2 cases (1.7%) of c-kit /PDGFRA wild type GISTs, the type of KRAS mutation was G12D and G12C, respectively. BRAFV600E mutation was found in 2 cases (1.7%) of wild type GISTs. No KRAS and BRAF mutations were found in the patients with the c-kit/PDGFRA mutation GISTs and pairs of GISTs before and after imatinib resistance. Two patients with KRAS mutation showed shorter progression free survivals for imatinib treatment. Two patients with BRAF mutation had longer recurrence free survivals. Conclusions Low frequency of KRAS or BRAF mutation only happens in wild type GISTs. KRAS mutation might be related to imatinib primary resistance, but not to secondary resistance.
ObjectiveTo investigate the predicting effect of PIK3CA mutations for the efficacy and prognosis of hepatocellular carcinoma (HCC) patients received surgical resection. MethodsPCR and DNA sequencing were used to detect the PIK3CA mutation status of 79 HCC tissues, its impact on the short and long term effects of the patients were analyzed. ResultsIn this group of patients, mutation rate of PIK3CA gene exon 9 was 39.24% (31/79), PIK3CA mutation rate correlated with lymph node status and tumor differentiation (P < 0.05). The therapeutic effect of patients with PIK3CA mutation was significantly poor than that of the non-mutated group (P < 0.05). The three-year cumulative survival of patients with PIK3CA mutation (33.33%) was significantly lower than non-mutated group's (60.00%) by Kaplan-Meier (P < 0.05). ConclusionPIK3CA gene mutation in exon 9 could impact the efficiency of surgical resection in patients with HCC and could predict a poor survival prognosis.
Mutations in the BEST1 gene are associated with a range of retinal diseases collectively referred to as "Best diseases", including Best vitelline macular dystrophy. More than 300 mutations at different sites of the BEST1 gene have been found, which may cause a series of functional disorders such as the mistransport of the calcium-activated anion channel protein-1 protein encoded by it, protein oligomerization defects, and abnormal anion channel activity, leading to different clinical phenotypes. Although it has been established that the BEST1 gene mutation is associated with at least one different type of Best disease, the relationship between the specific gene mutation site and the specific clinical phenotype has not been fully defined. For the time being. Drugs and gene therapy for the Best diseases are still in the basic research stage, which provides a broad development space for future treatment exploration. In the future, when selecting gene therapy in clinical applications, it is necessary to combine the clinical phenotype and molecular diagnosis of patients, and clearly define their mutation types and pathogenic mechanisms in order to achieve better personalized treatment effects.
ObjectiveTo investigate association between BRAFV600E gene mutation and extrathyroidal extension (ETE) among patients with papillary thyroid carcinoma (PTC).MethodsA retrospective study was conducted to collect all PTC surgical patients in the Renmin Hospital of Wuhan University from 2017 to 2019. The patients tested for BRAFV600E gene mutation were selected, and the association between BRAFV600E gene mutation and ETE were analyzed.ResultsThe BRAFV600E gene mutation test was performed only in 273 cases, 223 and 50 of whom were BRAFV600E gene with and without mutation, respectively; 194 and 79 of whom had ETE and no ETE, respectively. Univariate analysis showed that the incidence rate with BRAFV600E gene mutation was higher in the patients with ETE as compared with the patients without ETE (86.1% vs 70.9%, P=0.003) and the incidence rate of ETE was higher in the patients with BRAFV600E gene mutaton than in the patients without BRAFV600E gene mutaton (74.9% vs 54.0%, P=0.003). In addition, the incidence rates of ETE in the patients with tumor diameter >1 cm, bilaterality, and multifocality were higher than those in the patients with tumor diameter ≤1 cm (86.7% vs 61.3%, P<0.001), unilaterality (89.6% vs 63.8%, P<0.001), and single lesion (85.7% vs 60.9%, P<0.001), respectively. The incidence rate of ETE was increased with the increase of lymph node stage (P=0.003). Multivariate logistic regression analysis showed tumor size >1 cm [OR=3.606, 95%CI (1.758, 7.396), P<0.001], multifocality [OR=2.524, 95%CI (1.154, 5.519), P=0.020], with BRAFV600E gene mutaton [OR=3.022, 95%CI (1.443, 6.326), P=0.003] were the risk factors for ETE.ConclusionThe preliminary results of this study suggest that PTC patients with BRAFV600E gene mutaton are more likely to gross ETE.
Mutations in optic atrophy (OPA) genes can lead to a similar phenotype, namely optic atrophy, which can manifest as isolated optic atrophy or be accompanied by other systemic symptoms, mostly related to the nervous system. Currently, a total of 13 OPA genes have been discovered, covering a variety of inheritance patterns, including chromosomal dominant inheritance, autosomal recessive inheritance, and X-linked inheritance. Through genetic testing and analysis of patients, it is possible to accurately determine whether they carry mutation genes related to optic atrophy, and predict the progression of the disease and potential complications accordingly. This not only provides valuable genetic counseling and fertility planning guidance for patients and their families, but also helps better understand the disease, discover new therapeutic targets, and lay the foundation for developing more precise and effective drugs or gene therapies in the future.
ObjectiveTo summarize the progress in mutant gene sequences of different types of hereditary colorectal cancer.MethodThe relevant literatures about genetic mutations in hereditary colorectal cancer at home and abroad were reviewed.ResultsHereditary colorectal cancer coule be divided into two categories according to whether it was related to the germline mutations of known oncogenes. Among the known germline mutant genes, the gene of adenomatous polyposis coli (APC), MUTYH, thymidine glycol DNA glycosylase 1 (NTHL1), polymerase (DNA) epsilon, catalytic subunit (POLE), and polymerase (DNA) delta 1, catalytic subunit (POLD1) were closely related to adenomatous polyposis syndromes, mismatch repair (MMR)-related genes were related to Lynch syndrome, serine/threonine kinase 11 (STK-11) gene was related to Peutz-Jeghers syndrome, mutant genes of SMAD4 and bone morphogenetic protein receptor type 1A (BMPR1A) were found in JPS individuals, and Cowden syndrome was caused by phosphatase and tensin homology deleted on chromosome ten (PTEN) gene mutation. For colorectal cancer patients with unknown germline mutations but significant genetic characteristics (such as hyperplastic polyposis), relevant genes had also been gradually searched out, which needed further evidence.ConclusionsColorectal cancer is a malignant tumor with genetic characteristics. Compared with sporadic colorectal cancer, the time of hereditary colorectal cancer from adenoma to cancer is shorter, and the occurrence of heterogeneous tumor is also increased, but the survival rate after active intervention is higher than the sporadic one. To study the mutant gene sequences of hereditary colorectal cancer is the improvement and development of the diseases control in modern medicine.
ObjectiveTo investigate the correlation between histological subtypes of invasive lung adenocarcinoma and epithelial growth factor receptor (EGFR) gene mutation, and to provide a reference for clinical prediction of EGFR gene mutation status.MethodsFrom October 2017 to May 2019, 102 patients with invasive lung adenocarcinoma were collected, including 58 males and 44 females aged 62 (31-84) years. Invasive lung adenocarcinoma was classified into different histological subtypes. Scorpion probe amplification block mutation system (ARMS) real-time PCR was used to detect the mutation of EGFR gene in adenocarcinoma specimens, and the relationship between invasive lung adenocarcinoma subtypes and EGFR mutation status was analyzed.ResultsIn 102 patients with invasive lung adenocarcinoma, EGFR gene mutations were detected in 68 patients, and the mutation rate was 66.7% (68/102). The mutation sites were mainly concentrated in the exons 19 and 21; the mutation rate was higher in female patients (34/44, 77.3%) and non-smokers (34/58, 58.6%). EGFR mutation was mostly caused by acinar-like invasive lung adenocarcinoma, and was rare in solid-type lung adenocarcinoma. The EGFR gene mutation rates in different subtypes of adenocarcinoma were statistically different (P<0.05).ConclusionThe EGFR mutation status is related to gender, smoking status and histological subtype of invasive lung adenocarcinoma. EGFR mutation rates are higher in female, non-smoking and acinar-like invasive lung adenocarcinoma patients, and are lower in patients with solid type lung adenocarcinoma.
ObjectiveTo report the BEST1 gene mutations and clinical phenotypes in two pedigrees with Best vitelliform macular dystrophy (BVMD) and autosomal recessive bestrophinopathy (ARB)．MethodsA retrospective clinical study. From November 2019 to March 2021, in the Department of Ophthalmology of The First Affiliated Hospital of Zhengzhou University, the BVMD family (4 patients and 6 family members) and the ARB family (2 patients, 2 family members), a total of 6 patients and 8 normal family members were included in the study. Detailed medical history was obtained; best corrected visual acuity, fundus color photography, electrophysiology, optical coherence tomography and fundus autofluorescence examination were performed. The clinical characteristics for all patients in the two families were analyzed. Three milliliter peripheral venous blood of all participants in the family was collected, and the whole genomic DNA was extracted with gene sequencing using next-generation sequencing technology based on targeted capture. Compared with the database to identify the pathogenicity mutation sites, suspected pathogenic mutation sites were selected, then mutations in other members in the family was assayed by Sanger sequencing. ResultsIn family 1, the proband was demonstrated as typical BVMD, other patients were multifocal vitelliform macular dystrophy. The DNA sequencing result showed that all the 4 patients carried heterozygous missense mutations in exon 3 of BEST1 gene: c.240C>G (p.F80L) (M1) and 2 members carried this mutation, but without clinical phenotype. M1 was a likely-pathogenic mutation reported for the first time. In family 2, the proband and the other patient were diagnosed as ARB. The DNA result showed that the 2 patients carried heterozygous missense mutations in exon 5 and exon 2 of BEST1 gene: c.584C>T (p.A195V) (M2)、c.139C>A (p.R47S) (M3), and a heterozygous frameshift mutation in exon 3 of BEST1 gene: c.235dupT (p.S79Ffs*153) (M4). M2 was a pathogenic mutation reported previously. M3 variant was of undetermined significance. M4 was a first reported pathogenic mutation. ConclusionsThe BEST1 gene mutation is the main cause of BVMD and ARB. Different mutation sites have different clinical phenotypes. BVMD and ARB have genetic and clinical heterogeneity.
ObjectiveTo explore the genetic mutation characteristics, clinical manifestations, and treatment outcomes of catecholaminergic polymorphic ventricular tachycardia (CPVT), and to construct a quantitative scoring system for the severity of CPVT. The correlation between the mutations in different structural domains of the RyR2 gene and clinical manifestations and prognosis was analyzed. MethodsBy searching the PubMed and Web of Science databases for CPVT-related case reports published up to December 2024, data such as patient age, clinical manifestations, gene mutation sites, and treatment responses were collected. The quality of the literature was assessed using the CARE guidelines. The χ2 test was used to compare the severity and treatment response differences among different RyR2 structural domain mutation groups, and an innovative quantitative scoring system based on symptoms and efficacy was established. ResultsA total of 81 articles were included, with 102 patients in total. The quality of the literature was reliable. The age of the patients ranged from 1 to 84 years, with a higher proportion of children under 10 years old (25.5%). Female patients (55%) outnumbered males (45%). For CPVT patients, a quantitative scoring system was developed, with a total score of 2 to 10 points. Among them, 2 to 4 points were classified as mild, 5 to 7 points as moderate, and 8 to 10 points as severe. The results showed that severe patients often had a history of cardiac arrest and were resistant to treatment. Out of the 102 CPVT patients, RyR2 gene mutations accounted for 53.9% (55/81) of patients. Among them, the proportion of severe patients with N-terminal structural domain mutations was significantly higher than other regions, indicating that the RyR2 gene mutation structural domain has a significant impact on the severity of CPVT (χ2=17.530, P=0.008). The proportion of patients with mutations in the central hinge region who were ineffective with β-blockers reached 42.9% (3/7), which was significantly higher than other regions. Left cardiac sympathectomy was performed in 24 cases, and postoperative symptoms were almost completely controlled, significantly better than the drug treatment group. ConclusionMutations in the N-terminal structural domain of the RyR2 gene are significantly correlated with the severity of CPVT. Left cardiac sympathectomy has gradually become an effective intervention for refractory cases. The scoring system proposed in this study can provide a basis for clinical stratified treatment. In the future, there is a need to expand the sample size to verify mutation-specific treatment strategies.
In recent years, with the improvement of the sensitivity of examination equipment and the change of people's living environment and diet, the rate of thyroid cancer has risen rapidly, which has increased nearly five folds in 10 years. The pathogenesis, clinical manifestation, biological behavior, treatment and prognosis of thyroid carcinoma of different pathological types are obviously different. Papillary thyroid carcinoma (PTC) can develop at any age, which accounts for about 90% of thyroid cancer. It progresses slowly and has favourable prognosis, but lymph node metastasis appears easily. Whether PTC is accompanied by lymph node metastasis has an important impact on its prognosis and outcome. The Raf murine sarcoma viral oncogene homolog B(BRAF)gene mutation plays a crucial role in PTC lymph node metastasis. Having an in-depth understanding of the specific role and mechanism of BRAF gene mutation in PTC is expected to provide new ideas for diagnosis and treatment of PTC.