Next-generation sequencing assisted diagnosis of cervical metastasis in EGFR-mutated lung adenocarcinoma: A case report.
Ontology highlight
ABSTRACT:
SUBMITTER: Xu L
PROVIDER: S-EPMC8487810 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundThe efficacy of adjuvant targeted therapy for operable lung cancer is still under debate. Comprehensive genetic profiling is needed for detecting co-mutations in resected epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma (ADC), which may interfere the efficacy of adjuvant tyrosine kinase inhibitor (TKI) treatment.Materials and methodsMutation profiling of 416 cancer-relevant genes was conducted for 139 resected stage I-IIIa lung ADCs with EGFR mutations using targeted next-generation sequencing. Co-mutation profiles were systematically analyzed.ResultsRare EGFR alterations other than exon 19 deletion and L858R, such as L861Q (∼3%) and G719A (∼2%), were identified at low frequencies. Approximately 10% of patients had mutations in EGFR exon 20 that could confer resistance to first-generation TKIs. Ninety-one percent of patients harbored at least one co-mutation in addition to the major EGFR mutation. TP53 was the top mutated gene and was found more frequently mutated at later stage. Markedly, NF1 mutations were found only in stage II-III ADCs. Conversely, RB1 mutations were more frequent in stage I ADCs, whereas APC mutations were observed exclusively in this group. Thirty-four percent of patients with EGFR TKI-sensitizing mutations had genetic alterations involving EGFR downstream effectors or bypass pathways that could affect the response to EGFR TKIs, such as PIK3CA, BRCA1, and NOTCH1.ConclusionOperable lung ADCs with EGFR TKI-sensitizing mutations are associated with a high proportion of co-mutations. Mutation profiling of these resected tumors could facilitate in determining the applicability and efficacy of adjuvant EGFR TKI therapeutic strategy.Implications for practiceThe efficacy of adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy for lung cancer harboring EGFR mutation after surgical resection is still under debate. Next-generation sequencing of 416 cancer-relevant genes in 139 resected lung cancers revealed the co-mutational landscape with background EGFR mutation. Notably, the study identified potential EGFR TKI-resistant mutations in 34.71% of patients with a drug-sensitizing EGFR mutation and who were naive in terms of targeted therapy. A comprehensive mutation profiling of these resected tumors could facilitate in determining the applicability and efficacy of adjuvant EGFR TKI therapeutic strategy for these patients.
| S-EPMC6795151 | biostudies-literature
Project description:Although lung cancer rarely metastasizes to the breast, we report a case of breast metastasis from lung adenocarcinoma harboring an epidermal growth factor receptor mutation. This breast metastasis was initially considered recurrent breast cancer and was later diagnosed based on histopathological and molecular examinations as metastasis from lung cancer.
| S-EPMC6098998 | biostudies-literature
Project description:Somatic mutations in the EGFR proto-oncogene occur in ~15% of human lung adenocarcinomas and the importance of EGFR mutations for the initiation and maintenance of lung cancer is well established from mouse models and cancer therapy trials in human lung cancer patients. Recently, we identified DOK2 as a lung adenocarcinoma tumor suppressor gene. Here we show that genomic loss of DOK2 is associated with EGFR mutations in human lung adenocarcinoma, and we hypothesized that loss of DOK2 might therefore cooperate with EGFR mutations to promote lung tumorigenesis. We tested this hypothesis using genetically engineered mouse models and find that loss of Dok2 in the mouse accelerates lung tumorigenesis initiated by oncogenic EGFR, but not that initiated by mutated Kras. Moreover, we find that DOK2 participates in a negative feedback loop that opposes mutated EGFR; EGFR mutation leads to recruitment of DOK2 to EGFR and DOK2-mediated inhibition of downstream activation of RAS. These data identify DOK2 as a tumor suppressor in EGFR-mutant lung adenocarcinoma.
| S-EPMC3821857 | biostudies-literature
Project description:Introduction: Alveolar echinococcosis (AE) is a rare parasitic disease caused by the infection of Echinococcus multilocularis. AE may mimic malignancy both in clinical presentation and radiological imaging, which is often misdiagnosed as metastatic tumor. Recently, next-generation sequencing (NGS) technologies are increasingly being used to address a diverse range of biological questions. Here, we describe a rare case of alveolar echinococcosis diagnosed by pan-pathogen screening, using next-generation sequencing. To the best of our knowledge, this is the first reported case of AE which was definitely diagnosed relying NGS of cerebrospinal fluid (CSF). Case Presentation: A 33-year-old man presented with repeat seizure and progressive headache for six months. Head magnetic resonance imaging (MRI) showed multiple masses with edema. Lung and abdominal computer tomography (CT) revealed multiple masses in bilateral lung, liver and the right adrenal gland. Bacterial, tuberculosis and fungal infection were excluded by CSF examination. Repeated target biopsy on the masses in the lung and liver showed as fibrous connective tissue without positive findings. NGS of CSF was performed and detected nucleic acid sequences of E. multilocularis. Consequently, the patient has accepted 1-year albendazole therapy. His case was followed up through imaging procedures. Conclusion: The next-generation sequencing of CSF is a reliable and sensitive diagnostic method for the detection of pathogenic microorganisms, and may allow the accurate diagnosis of alveolar echinococcosis. In view of this case, we recommend NGS as a potential tool for diagnosis of cerebral AE, especially if repeated biopsies are negative.
| S-EPMC8299116 | biostudies-literature
Project description:BACKGROUND:Scrub typhus is an acute febrile illness, which was caused by Orientia tsutsugamushi and transmitted through the bite of chiggers. The diagnosis of scrub typhus could be missed diagnosis due to the absence of the pathognomonic eschar. CASE PRESENTATION:A 76-year-old man was hospitalized with fever and kidney injury and was diagnosed of hemorrhagic fever with renal syndrome first. However, the situation of the illness deteriorated into refractory septic shock and multiple organ dysfunction rapidly,although the treatment of anti-sepsis was used in 3rd-5th day. Orientia tsutsugamushi was determined to be the causative pathogen by Next-generation sequencing of his plasma sample in 6th day. Then, the patient was treated with doxycycline and azithromycin and recovered quickly. CONCLUSIONS:Next-generation sequencing was a new diagnostic technology and could identify scrub typhus in accurately and fast without the pathognomonic eschar.
| S-EPMC7137524 | biostudies-literature
Project description:The discovery that mutations in the EGFR gene are detected in up to 50% of lung adenocarcinoma patients, along with the development of highly efficacious epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), has revolutionized the treatment of this frequently occurring lung malignancy. Indeed, the clinical success of these TKIs constitutes a critical milestone in targeted cancer therapy. Three generations of EGFR-TKIs are currently approved for the treatment of EGFR mutation-positive non-small cell lung cancer (NSCLC). The first-generation TKIs include erlotinib, gefitinib, lapatinib, and icotinib; the second-generation ErbB family blockers include afatinib, neratinib, and dacomitinib; whereas osimertinib, approved by the FDA on 2015, is a third-generation TKI targeting EGFR harboring specific mutations. Compared with the first- and second-generation TKIs, third-generation EGFR inhibitors display a significant advantage in terms of patient survival. For example, the median overall survival in NSCLC patients receiving osimertinib reached 38.6 months. Unfortunately, however, like other targeted therapies, new EGFR mutations, as well as additional drug-resistance mechanisms emerge rapidly after treatment, posing formidable obstacles to cancer therapeutics aimed at surmounting this chemoresistance. In this review, we summarize the molecular mechanisms underlying resistance to third-generation EGFR inhibitors and the ongoing efforts to address and overcome this chemoresistance. We also discuss the current status of fourth-generation EGFR inhibitors, which are of great value in overcoming resistance to EGFR inhibitors that appear to have greater therapeutic benefits in the clinic.
| S-EPMC8454558 | biostudies-literature
Project description:Identification of multi-gene variations has led to the development of new targeted therapies in lung adenocarcinoma patients, and identification of an appropriate patient population with a reliable screening method is the key to the overall success of tumor targeted therapies. In this study, we used the Ion Torrent next-generation sequencing (NGS) technique to screen for mutations in 89 cases of lung adenocarcinoma metastatic lymph node specimens obtained by fine-needle aspiration cytology (FNAC). Of the 89 specimens, 30 (34%) were found to harbor epidermal growth factor receptor (EGFR) kinase domain mutations. Seven (8%) samples harbored KRAS mutations, and three (3%) samples had BRAF mutations involving exon 11 (G469A) and exon 15 (V600E). Eight (9%) samples harbored PIK3CA mutations. One (1%) sample had a HRAS G12C mutation. Thirty-two (36%) samples (36%) harbored TP53 mutations. Other genes including APC, ATM, MET, PTPN11, GNAS, HRAS, RB1, SMAD4 and STK11 were found each in one case. Our study has demonstrated that NGS using the Ion Torrent technology is a useful tool for gene mutation screening in lung adenocarcinoma metastatic lymph node specimens obtained by FNAC, and may promote the development of new targeted therapies in lung adenocarcinoma patients.
| S-EPMC4464150 | biostudies-other
Project description:BACKGROUND:Osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor, is selective for both epidermal growth factor receptor tyrosine kinase inhibitor-sensitizing and T790M resistance mutations. Almost all patients who initially respond to an epidermal growth factor receptor tyrosine kinase inhibitor subsequently report disease progression. Epidermal growth factor receptor-dependent resistance mechanisms, bypass pathway activation, and histological transformation have been reported with osimertinib therapy. CASE PRESENTATION:We report a case of a 64-year-old Asian man with epidermal growth factor receptor T790M-positive adenocarcinoma that transformed to epidermal growth factor receptor T790M-negative large-cell neuroendocrine carcinoma after osimertinib therapy. A prompt rebiopsy revealed a rare mechanism of resistance to epidermal growth factor receptor tyrosine kinase inhibitor, and subsequently treatment with carboplatin and etoposide was effective. CONCLUSIONS:Despite the promising emergence of circulating tumoral DNA testing, this case report emphasizes the importance of rebiopsy of a progressive epidermal growth factor receptor-mutant tumor.
| S-EPMC7412784 | biostudies-literature
Project description:BackgroundTargeted therapies have improved survival and quality of life for patients with non-small-cell lung cancer with actionable driver mutations. However, epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 gene (HER2, also known as ERBB2) exon 20 insertions (Ex20mut) are characterized by a poor response to currently approved tyrosine kinase inhibitors and immunotherapies. The underlying immune biology is not well understood.Materials and methodsWe carried out messenger RNA expression profiling of lung adenocarcinomas (ADCs) with ERBB2 (n = 19) and EGFR exon 20-insertion mutations (n = 13) and compared these to tumors with classical EGFR mutations (n = 40, affecting EGFR exons 18, 19 or 21) and EGFR/ERBB2 mutation-negative lung ADC (EGFR/ERBB2wt, n = 26) focusing on immunologically relevant transcripts. Tumor-infiltrating immune cells were estimated from gene expression profiles.ResultsCytotoxic cells were significantly lower in EGFR-mutated tumors regardless of the affected exon, while Th1 cells were significantly lower in EGFR-Ex20mut compared to EGFR/ERBB2wt tumors. We assessed the differentially expressed genes of ERBB2-Ex20mut and EGFR-Ex20mut tumors compared to EGFR-Ex18/19/21mut and EGFR/ERBB2wt tumors. Of these, the genes GUSB, HDAC11, IFNGR2, PUM1, RASGRF1 and RBL2 were up-regulated, while a lower expression of CBLC, GBP1, GBP2, GBP4 and MYC was observed in all three comparison groups. The omnibus test revealed 185 significantly (FDR = 5%) differentially expressed genes and we found these four most significant gene expression changes in the study cohort: VHL and JAK1 were overexpressed in ERBB2-Ex20mut and EGFR-Ex20mut tumors compared to both EGFR-Ex18/19/21mut and EGFR/ERBB2wt tumors. RIPK1 and STK11IP showed the highest expression in ERBB2-Ex20mut tumors.ConclusionsTargeted gene expression profiling is a promising tool to read out the characteristics of the tumor microenvironment from routine diagnostic lung cancer biopsies. Significant immune reactivity and specific immunosuppressive characteristics in ERBB2-Ex20mut and EGFR-Ex20mut lung ADC with at least some degree of immune infiltration support further clinical evaluation of immune-modulators as partners of immune checkpoint inhibitors in such tumors.
| S-EPMC8426209 | biostudies-literature
Project description:The EGFR gene was one of the first molecules to be selected for targeted gene therapy. EGFR-mutated lung adenocarcinoma, which is responsive to EGFR inhibitors, is characterized by a distinct oncogenic pathway in which unique microRNA (miRNA)⁻mRNA interactions have been observed. However, little information is available about the miRNA⁻mRNA regulatory network involved. Both miRNA and mRNA expression profiles were investigated using microarrays in 155 surgically resected specimens of lung adenocarcinoma with a known EGFR mutation status (52 mutated and 103 wild-type cases). An integrative analysis of the data was performed to identify the unique miRNA⁻mRNA regulatory network in EGFR-mutated lung adenocarcinoma. Expression profiling of miRNAs and mRNAs yielded characteristic miRNA/mRNA signatures (19 miRNAs/431 mRNAs) in EGFR-mutated lung adenocarcinoma. Five of the 19 miRNAs were previously listed as EGFR-mutation-specific miRNAs (i.e., miR-532-3p, miR-500a-3p, miR-224-5p, miR-502-3p, and miR-532-5p). An integrative analysis of miRNA and mRNA expression revealed a refined list of putative miRNA⁻mRNA interactions, of which 63 were potentially involved in EGFR-mutated tumors. Network structural analysis provided a comprehensive view of the complex miRNA⁻mRNA interactions in EGFR-mutated lung adenocarcinoma, including DUSP4 and MUC4 axes. Overall, this observational study provides insight into the unique miRNA⁻mRNA regulatory network present in EGFR-mutated tumors. Our findings, if validated, would inform future research examining the interplay of miRNAs and mRNAs in EGFR-mutated lung adenocarcinoma.
| S-EPMC6262391 | biostudies-literature