Objective To further strengthen the understanding of the genesis of thyroid tumors through the analysis of thyroid nodules in the clonal origin. Method The related literatures which discussed the clonality of thyroid nodules were reviewed and analyzed. Results About the clonal origin of thyroid nodules， the X chromosome inactivation detection and single gene mutation detection were the most widely chosen one at present. Most of the materials available at present related to X chromosome inactivation proposed that major part of the thyroid nodules were monoclonal and the malignant cells spreaded by means of the inner lymphatic vessel net，whereas polyclonal and monoclonal thyroid nodules coexisted occasionally. Only BRAF mutation was found of certain importance in clonal origin identification in the thyroid nodules. Conclusions Thyroid nodule is prevalent in clinical practice，while the clonality of thyroid nodules especially the thyroid tumor is not clear. And for the time being the commonly used methods to identify the clonal origin of thyroid nodule are X chromosome inactivation and single gene mutation detection. Published results confirm the finding of X chromosome inactivation methods that the majority of thyroid nodules are monoclonally originated.
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 observe the clinical features of eyes in children with methylmalonic acidemia (MMA). MethodsA retrospective clinical case study. From June 2019 to June 2022, 13 children with MMA visited on the Department of Ophthalmology of Henan Children's Hospital were included in the study. The anterior segment and fundus were examined under surface or general anesthesia. Best corrected visual acuity (BCVA) and refraction were performed in 9 cases; fluorescein fundus angiography (FFA) was performed in 3 cases; flash electroretinogram (FERG) was performed in 6 cases; flash visual evoked potential (FVEP) was detected in 6 cases; optical coherence tomography (OCT) was performed in 3 cases. ResultsAmong the 13 pediatric patients with methylmalonic acidemia, 6 cases were male and 7 cases were female. The average age at first visit was 45 months. All cases suffered from hyperhomocysteinemia; 9 cases were with epilepsy; 2 cases were with infantile spasms; 11 cases were with stunting, 13 cases were with repeated pulmonary infection during growth period; 4 cases were with hydrocephalus; 1 cases was with hypertension and renal insufficiency. Genetic dectection results of 8 cases were recorded, MMACHC:c.609G>A:p.W203* mutation site was found in all cases. One case was accompanied by corneal ulcer. There were 10 cases with nystagmus, 4 cases with macular degeneration, 3 cases with hyperopic refractive error and esotropia. Nine cases underwent BCVA examination, BCVA was light perception-0.6. In OCT, 2 cases of 3 cases showed retinal thinning and photoreceptor cell layer atrophy in the macular area. In FFA, 2 cases of 3 cases showed circular transparent fluorescence in the macular area. Five cases of 6 cases who with FVEP had different degrees of P100 peak time delay and decreased amplitude, and 4 cases of 6 cases with FERG had decrease of a and b wave in light and dark adaptation. ConclusionsThe clinical phenotypes of eyes in children with MMA are various and the severity was different; most of them are accompanied by nystagmus, and the fundus lesions are common in the characteristic bovine eye like macular region. Those with macular disease have severe visual impairment.
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.
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.
Objective To investigate clinicopathologic features, pathogenesis, and diagnosis and treatment of hereditary pancreatitis (HP). Method The relevant literatures on HP research in recent years were searched and reviewed. Results The HP was similar to the pancreatitis caused by the cholelithiasis, excessive alcohol consumption, hyperlipidemia, etc. in the histomorphology, function, and clinical manifestations and it was difficult to be distinguished. However, HP was different from the other types of chronic pancreatitis due to its early onset, familial, and high risk of pancreatic cancer. The HP was mainly caused by the PRSS1 mutations, and its mutation types mainly included the R122H, N29I, A16V, K23R, etc., among which the R122H and N29I were the two most common types of mutations. There was no specific treatment for the HP. The principles of treatment of HP were similar to the pancreatitist caused by other etiologies, including the nutritional support, blood sugar control, analgesia, etc.. In addition to the medical treatment, the surgical intervention was also the important means for the treatment of HP, including the pancreatic partial resection, total pancreatectomy or total pancreatectomy combined with islet cell autografting. Conclusions HP is an autosomal dominant hereditary disease characterized by recurrent attacks of pancreatitis. Relevant gene tests could be performed for patient with highly suspected HP. It faces great challenges in treatment of HP. Pathogenesis of HP needs to be constantly explored and experimental study of multicenter and large sample needs to be further studied in order to determine its best treatment strategy.
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.
Objective To examined gene mutations in thymic carcinoma (TC) patients and to explore prognostic correlates and potential targets for therapy. MethodsWe retrospectively included TC patients in Sichuan Cancer Hospital between January 2015 and Febuary 2021.Whole-exome sequencing was performed on tumor tissues from TC patients and their control peripheral blood samples, and the raw data were subjected to bioinformatics analysis and statistical analysis. Results We finally included 24 TC patients with 16 males and 8 females at a median age of 55 (42-74) years. The highest frequency of single nucleotide mutations in this cohort were in the TTN gene (42%), HSPG2 (29%), and OBSCN (29%). Higher frequency of copy number variations occurred in ZNF276 gene (54%, loss), BEND3 (50%, loss), DHODH (50%, loss), and VAC14 (50%, loss). Microsatellite instability (MSI) phenotype was found in 25% of the patients, and the mean tumor mutation burden (TMB) was 9.86. Conclusion This study is the first comprehensive analysis of the mutation profile of thymic carcinoma in China to date. The mutation frequencies of TTN, OBSCN, and ZNF276 genes were high. The biomarker analysis suggests that patients may benefit from immunotherapy and have a long effective survival.
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.