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.
ObjectiveTo investigate research advance on the value of B-type RAF kinase (BRAF) gene mutation assisted diagnosis of papillary thyroid cancer (PTC) in thyroid nodule.MethodThe recent literatures on the BRAF gene mutation and its combination with fine needle aspiration cytology (FNAC) in the diagnosis of benign and malignant thyroid nodules and PTC were collected and reviewed.ResultsThe BRAFV600E gene mutation was the most common type of gene mutation in the genetic molecule of PTC. The combination of the FNAC and BRAF gene mutation detection could improve the diagnostic value of the benign and malignant thyroid nodules, especially the diagnostic accuracy of PTC. However, the negative detection of BRAF gene mutation did not rule out the possibility of PTC. It still remained controversial that the detection of BRAF gene mutation could differentiate between the benign and malignant thyroid nodules.ConclusionsBRAF gene mutation detection has different diagnostic values in different types of thyroid nodules. It has considerable diagnostic value in thyroid nodules with high BRAF mutation incidence (suspicious for malignancy, undetermined significance or follicular lesion of undetermined significance nodules) while presents false negative result in thyroid nodule with very low mutation incidence category to a large extent. BRAF gene detection might become a specific diagnostic molecular marker to promote diagnosis accuracy of PTC.
Objective
To analyze the relationship between the epidermal growth factor receptor(EGFR) gene mutation and malignant pulmonary focal ground-glass lesion (fGGL).
Methods
We retrospectively collected the clinical data of 86 patients with surgical treatment in the department of cardiothoracic surgery of Changzheng Hospital from August 2012 to February 2015. There were 26 males and 60 females with a mean age of 56.14±10.55 years. We analyzed the relationship between the EGFR gene mutation and the related clinical data.
Results
Postoperative pathology showed atypical adenomatous hyperplasia (AAH) combined with focal adenocarcinoma in situ (AIS) or AIS in 10 patients, minimally invasive adenocarcinoma (MIA) in 15, and lepidic predominant adenocarcinoma (LPA) in 61. The EGFR gene mutation reports showed the exon 19 19-del mutation in 14 patients, exon 21 L858R mutation in 27, and exon 21 L861Q mutation in 2. There was no difference between the mutation of EGFR gene and clinical factors except age and smoking (P>0.05). Till June 30, 2015, all patients were alive and follow-up was 440.48±186.61 days.
Conclusion
The EGFR gene in patients with malignant pulmonary fGGL shows a higher mutation rate, which provides important clinical reference data for the basic research and the clinical treatment.
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 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.
ObjectiveTo study the relation between the clinical phenotype and neurological developmental quotient in children with epilepsy and GPR98 gene mutation.
MethodsGenomic DNA was extracted from peripheral blood lymphocytes of the probands and other available members in the epilepsy families.Clinical datas and screened for mutations by next-generation sequencing conbined target sequencing technology and PCR and direct DNA sequencing were collected.Then, the relations between the clinical phenotype and developmental quotient in children with epilepsy and GPR98 gene mutation was analyzed.
ResultsSeven novel GPR98 gene mutations were found in seven probands in 65 families, including six heterozygote missense mutations (c.6083C <、c.1969A < C、c.17531C < T、c.9069G < C、c.6661G < A and c.18496A < C) and one nonsense mutation (c.14224G < T). One of their parents carried the same GPR98 gene mutation as the proband's. The initial symptom of six cases was afebrile seizures and one showed febrile seizure, in which the main type seizure was generalized seizure.Moreover, was were significant difference between children with epilepsy and GPR98 gene mutations and healthy children in developmental quotient test(P < 0.01).
ConclusionsThe main type of seizures in children with epilepsy and GPR98 gene mutations is generalized seizure. Furthermore, GPR98 gene mutations may be associated with psychomotor retardation.
Lung cancer is a most common malignant tumor of the lung and is the cancer with the highest morbidity and mortality worldwide. For patients with advanced non-small cell lung cancer who have undergone epidermal growth factor receptor (EGFR) gene mutations, targeted drugs can be used for targeted therapy. There are many methods for detecting EGFR gene mutations, but each method has its own advantages and disadvantages. This study aims to predict the risk of EGFR gene mutation by exploring the association between the histological features of the whole slides pathology of non-small cell lung cancer hematoxylin-eosin (HE) staining and the patient's EGFR mutant gene. The experimental results show that the area under the curve (AUC) of the EGFR gene mutation risk prediction model proposed in this paper reached 72.4% on the test set, and the accuracy rate was 70.8%, which reveals the close relationship between histomorphological features and EGFR gene mutations in the whole slides pathological images of non-small cell lung cancer. In this paper, the molecular phenotypes were analyzed from the scale of the whole slides pathological images, and the combination of pathology and molecular omics was used to establish the EGFR gene mutation risk prediction model, revealing the correlation between the whole slides pathological images and EGFR gene mutation risk. It could provide a promising research direction for this field.
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 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.
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.
