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.
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.
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 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.
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.
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 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 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.
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.
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.
