scholarly journals PATH-35. RETROSPECTIVE ANALYSIS OF 145 PATIENTS WITH GLIOBLASTOMA; CORRELATING MOLECULAR ALTERATION INCIDENCE WITH DEMOGRAPHICS, TUMOR LOCATION, AND PROGNOSIS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi150-vi151
Author(s):  
Mina Lobbous ◽  
ZacK Tucker ◽  
Elizabeth Coffee ◽  
Louis Nabors
Keyword(s):  
Progression Free Survival ◽  
Tumor Location ◽  
Genetic Alterations ◽  
Primary Brain Tumor ◽  
Demographic Variables ◽  
The Cancer Genome Atlas ◽  
Missense Mutations ◽  
Molecular Alteration ◽  
Molecular Alterations ◽  
Cdkn2a Deletion

Abstract Glioblastoma is the most common and most aggressive primary brain tumor in adults. Glioblastoma was the first neoplasm to be systemically studied by The Cancer Genome Atlas and is one of the most molecularly well-characterized tumors in humans. Molecular profiling of glioblastoma is increasingly available and had led to the identifications of multiple prognostic factors as well as potential actionable targets for novel therapies. We identified 145 patients diagnosed with glioblastoma whose tumor tissue was analyzed using next generation sequencing (NGS). The NGS was performed using validated, commercially available panels. We studied somatic genetic alterations with a particular focus on TERT (which was altered in 55.9% of patients in the dataset), CDKN2A (44%), TP53 (39%), EGFR (38.6%), PTEN (31%), IDH1 (20%), and CDK4 (9%). These molecular alterations were analyzed in relation to the patients’ tumor locations, demographics, and outcomes. We used multiple binary logistic regressions to assess whether demographics and tumor location were predictive of the above alterations We also assessed the relationship between molecular alterations and outcomes when controlling for treatment and demographic variables. Among demographic variables, age predicted alterations in IDH1, EGFR, TERT, TP53, and PTEN. Frontal lobe tumors were more likely to be IDH1-mutated, irrespective of patient age. Sex and race did not predict the incidence of the molecular alterations of interest. Analysis of outcomes revealed that, when controlling for treatment and demographic variables, TERT promoter mutations, TP53 nonsense mutations, and EGFR A289V were predictive of a decreased progression-free survival, while CDKN2A deletion, PTEN missense mutations, and EGFR A289V were predictive of decreased overall survival. Our experience highlights the importance of incorporating routine NGS in the management of patients with glioblastoma. More studies are required to evaluate the predictive and/or prognostic values of different molecular alterations.

Colorectal cancer: Impact of primary tumor location on genetic alterations.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3578-3578 ◽  
Author(s):  
Mohamed E. Salem ◽  
Heinz-Josef Lenz ◽  
Joanne Xiu ◽  
Jimmy J. Hwang ◽  
Philip Agop Philip ◽  
...  
Keyword(s):  
Tumor Location ◽  
Genetic Alterations ◽  
Hepatic Flexure ◽  
Missense Mutations ◽  
Chi Square ◽  
Molecular Alterations ◽  
Clear Cut ◽  
Comparison Results ◽  
Her 2 ◽  
The Right

3578 Background: Recent data show that patients with left sided colon tumors (LT) have better survival and respond differently to biologics compared to patients with right-sided tumors (RT), likely due to molecular differences. We sought to examine these differences. Methods: Primary colorectal tumors (n = 1730) with origins clearly defined as RT (cecum to hepatic flexure; n = 273), LT (splenic flexure to sigmoid colon; n = 585), or rectal (RC; n = 872) were examined by NextGen sequencing, protein expression and gene amplification. Tumor mutational load (TML) was calculated in 1001 of these tumors using only somatic nonsynonymous missense mutations. Chi-square was used for comparison. Results: When compared to LT, RT carried a significantly higher rate of BRAF (25% vs 7%; p < 0.0001), PTEN (5.4% vs 1.3%; p = 0.008), and ATM (4% vs 1%; p = 0.04) mutations. RT were likely to have more MSI-high tumors (22% vs 5%; p < 0.0001) and PD-1 overexpression (58% vs 44%; p = 0.01). There were no differences in the rate of KRAS (50% vs 42%; p = 0.07) or NRAS mutations (2.2% vs 3.4%; p = 0.4). When compared to RC, RT had a higher rate of BRAF (25% vs 3%; p = 7E-07), PIK3CA (22% vs 11%; p = 0.001), CTNNB1 (3% vs 0.3%; p = 0.02); ATM (3% vs 1%; p = 0.04), PTEN (5% vs 1%; p = 0.004), and BRCA1 mutations (4% vs 0%; p = 0.02), and a lower rate of TP53 (56% vs 71%; p = 0.001) and APC (53% vs 66%; p = 0.003) mutations. When compared to RC, LT showed higher rates of BRAF (6.7% vs 3.2%; p = 0.04) and CTNNB1 (2.1% vs 0.3%; p = 0.04) mutations, and a higher rate of MSI-high tumors (4.6% vs 0.7%; p = 0.04), whereas RC had a higher rate of KRAS mutation (50% vs 42%; p = 0.04). There were no differences between RT, LT, and RC for the frequency of PD-L1 (2%, 2%, and 1%) or Her-2 (1%, 2%, and 3%) overexpression, although Her-2 amplification was significantly different (1%, 3%, and 5%, RT vs RC; p = 0.03). Mean TML was 12, 11, and 8 mutations/megabase for RT, LT, and RC, respectively (RT vs RC; p = 0.01). There was a correlation between TML and PD-L1 (p = 0.04) and PD-1 (p = 0.01). Conclusions: Tumors arising in the right colon carry genetic alterations that are different from LT as well as RC. However, it appears that CRCs carry a continuum of molecular alterations from the right to the left side, rather than displaying sharp, clear-cut differences.

scholarly journals Clinical impact of combined epigenetic and molecular analysis of pediatric low-grade gliomas

2020 ◽  
Vol 22 (10) ◽  
pp. 1474-1483 ◽  
Author(s):  
Kohei Fukuoka ◽  
Yasin Mamatjan ◽  
Ruth Tatevossian ◽  
Michal Zapotocky ◽  
Scott Ryall ◽  
...  
Keyword(s):  
Molecular Analysis ◽  
Progression Free Survival ◽  
Lymphocytic Infiltration ◽  
Tumor Location ◽  
Genetic Alterations ◽  
Pleomorphic Xanthoastrocytoma ◽  
Low Grade ◽  
Low Grade Gliomas ◽  
Additional Information ◽  
Molecular Alterations

Abstract Background Both genetic and methylation analysis have been shown to provide insight into the diagnosis and prognosis of many brain tumors. However, the implication of methylation profiling and its interaction with genetic alterations in pediatric low-grade gliomas (PLGGs) are unclear. Methods We performed a comprehensive analysis of PLGG with long-term clinical follow-up. In total 152 PLGGs were analyzed from a range of pathological subtypes, including 40 gangliogliomas. Complete molecular analysis was compared with genome-wide methylation data and outcome in all patients. For further analysis of specific PLGG groups, including BRAF p.V600E mutant gliomas, we compiled an additional cohort of clinically and genetically defined tumors from 3 large centers. Results Unsupervised hierarchical clustering revealed 5 novel subgroups of PLGG. These were dominated by nonneoplastic factors such as tumor location and lymphocytic infiltration. Midline PLGG clustered together while deep hemispheric lesions differed from lesions in the periphery. Mutations were distributed throughout these location-driven clusters of PLGG. A novel methylation cluster suggesting high lymphocyte infiltration was confirmed pathologically and exhibited worse progression-free survival compared with PLGG harboring similar molecular alterations (P = 0.008; multivariate analysis: P = 0.035). Although the current methylation classifier revealed low confidence in 44% of cases and failed to add information in most PLGG, it was helpful in reclassifying rare cases. The addition of histopathological and molecular information to specific methylation subgroups such as pleomorphic xanthoastrocytoma–like tumors could stratify these tumors into low and high risk (P = 0.0014). Conclusion The PLGG methylome is affected by multiple nonneoplastic factors. Combined molecular and pathological analysis is key to provide additional information when methylation classification is used for PLGG in the clinical setting.

scholarly journals Expression of Human Epidermal Growth Factor Receptor-2 Status and Programmed Cell Death Protein-1 Ligand Is Associated With Prognosis in Gastric Cancer

2021 ◽  
Vol 10 ◽  
Author(s):  
Huifang Lv ◽  
Junling Zhang ◽  
Keran Sun ◽  
Caiyun Nie ◽  
Beibei Chen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
Checkpoint Inhibitors ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Underlying Mechanism ◽  
Tumor Location ◽  
The Cancer Genome Atlas ◽  
Prognostic Indicators ◽  
Her 2

BackgroundPD-L1 and HER-2 are routine biomarkers for gastric cancer (GC). However, little research has been done to investigate the correlation among PD-L1, HER-2, immune microenvironment, and clinical features in GC.MethodsBetween January 2013 and May 2020, a total of 120 GC patients treated with chemotherapy were admitted to Henan Tumor Hospital. We retrospectively identified PD-L1, HER-2 level before chemotherapy and abstracted clinicopathologic features and treatment outcomes. Univariate and multivariate survival analyses were performed to assess the relationship between PD-L1/HER-2 levels and progression-free survival (PFS). The mRNA and tumor microenvironment of 343 patients with GC from The Cancer Genome Atlas (TCGA) were used to explore the underlying mechanism.ResultsWe retrospectively analyzed 120 patients with gastric cancer, including 17 patients with HER-2 positive and 103 patients with HER-2 negative GC. The results showed that the expression of PD-L1 was closely correlated with HER-2 (P = 0.015). Patients with PD-L1/HER-2 positive obtained lower PFS compared to PD-L1/HER-2 negative (mPFS: 6.4 vs. 11.1 months, P = 0.014, mPFS: 5.3 vs. 11.1 months, P = 0.002, respectively), and the PD-L1 negative and HER-2 negative had the best PFS than other groups (P = 0.0008). In a multivariate model, PD-L1 status, HER-2 status, tumor location, and tumor differentiation remained independent prognostic indicators for PFS (P &lt; 0.05). The results of database further analysis showed that the proportion of PD-L1+/CD8A+ in HER-2 negative patients was higher than that in HER-2 positive patients (37.6 vs 20.3%), while PD-L1−/CD8A− was significantly higher in HER-2 positive patients than HER-2 negative patients (57.8 vs. 28.8%). In addition, it showed that not only CD4+T cells, macrophages, and CD8+T cells, but also the associated inflammatory pathways such as IFN-γ/STAT1 were associated with HER-2.ConclusionHER-2 status could predict the efficacy of immune checkpoint inhibitors, and HER-2 status combined with PD-L1 level could predict the prognosis of GC patients.

scholarly journals FOXL2 expression might be a novel prognostic biomarker in patients with laryngeal squamous cell carcinoma

2020 ◽  
Vol 48 (4) ◽  
pp. 030006052091925
Author(s):  
Jun Ge ◽  
Li Jiang ◽  
Yuke Tian ◽  
Min Zheng ◽  
Meiling Huang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Prognostic Biomarker ◽  
Dna Amplification ◽  
Progression Free Survival ◽  
Genetic Alterations ◽  
The Cancer Genome Atlas ◽  
Gene Body

Objectives This study aimed to explore the expression profile of the Forkhead box protein L2 gene ( FOXL2) and to determine its prognostic value and associated epigenetic and genetic alterations in patients with laryngeal squamous cell carcinoma (LSCC). Materials and methods Data for a subset of patients with LSCC (N = 116) were extracted from the head and neck squamous cell carcinoma dataset of The Cancer Genome Atlas and analyzed in relation to FOXL2 expression and survival. Results Aberrant FOXL2 expression was an independent prognostic factor for progression-free survival (PFS) (hazard ratio (HR): 2.63, 95% confidence interval (CI): 1.34–5.18) and overall survival (OS) (HR: 2.39, 95%CI: 1.28–4.46). Two gene-body CpG sites (cg10554436 and cg23637494) were moderately and positively correlated with FOXL2 expression. DNA amplification (+2/+1) was common (82/115, 71%) in LSCC, and FOXL2 expression was significantly upregulated in the high-amplification group (+2) compared with copy-neutral (0) cases. Conclusion Aberrant FOXL2 expression may be a novel prognostic biomarker for PFS and OS among patients with LSCC. FOXL2 upregulation may be related to gene-body hypermethylation and DNA amplification.

Bladder cancer genomics

2020 ◽  
Vol 87 (2) ◽  
pp. 49-56
Author(s):  
Salvatore Siracusano ◽  
Riccardo Rizzetto ◽  
Antonio Benito Porcaro
Keyword(s):  
Bladder Cancer ◽  
Cancer Genomics ◽  
Treatment Strategies ◽  
Genetic Alterations ◽  
Point Of View ◽  
The Cancer Genome Atlas ◽  
Molecular Alterations ◽  
Cancer Genome Atlas ◽  
Polymerase Chain ◽  
Muscle Invasive

Until recently, the treatment of bladder cancer, for several years, was limited to surgery and to immunotherapy or chemotherapy. Currently, the extensive analysis of molecular alterations has led to novel treatment approaches. The advent of polymerase chain reaction and genomic hybridization techniques has allowed to investigate alterations involved in bladder cancer at DNA level. By this way, bladder cancers can be classified as papillary or non-papillary based on genetic alterations with activation or mutations in FGFR3 papillary tumors and with inactivation or mutations involving TP53 and RB1 in non-papillary tumors. Recently, the patterns of gene expression allow to differentiate basal and luminal subtypes as reported in breast cancer. In particular, basal cancers are composed of squamous and sarcomatoid pathological findings, while luminal cancers are composed of papillary finding features and genetic mutations (FGFR3). In particular, specific investigative studies demonstrated that luminal cancers are associated with secondary muscle invasive cancer while basal tumors are related to advanced disease since they are often metastatic at diagnosis. Moreover, from therapeutic point of view, different researchers showed that mutations of DNA are related to the sensitivity of bladder cancer while performing cisplatin chemotherapy. In this prospective, the bladder cancer molecular subtyping classification might allow identifying the set of patients who can safely avoid neoadjuvant chemotherapy likely because of the low response to systemic chemotherapy (chemoresistant tumors). In this context, the Cancer Genome Atlas (TCGA) project has improved the knowledge of the molecular targets of invasive urothelial cancers allowing the researchers to propose hypothesis suggesting that agents targeting the genomic alterations may be an effective strategy in managing these cancers, which occur in about 68% of muscle invasive cancers. A future goal will be to combine treatment strategies of invasive bladder cancers according to their genetic mutational load defined by molecular pathology.

scholarly journals Genetic alterations and functional networks of m6A RNA methylation regulators in pancreatic cancer based on data mining

2021 ◽  
Author(s):  
Juan Zeng ◽  
Heying Zhang ◽  
Yonggang Tan ◽  
Zhe Wang ◽  
Yunwei Li ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Messenger Rna ◽  
Genetic Alterations ◽  
The Cancer Genome Atlas ◽  
Rna Modification ◽  
Functional Networks ◽  
Molecular Alterations ◽  
M6a Rna Methylation ◽  
Molecular Therapeutic ◽  
New Strategies

Abstract Background Pancreatic cancer is a fatal malignancy of the digestive system and the 5-year survival rate remains low. Therefore, new molecular therapeutic targets are required to improve treatments, prognosis, and the survival of patients. N6-methyladenosine (m6A) is the most prevalent reversible methylation in mammalian messenger RNA (mRNA) and has critical roles in the tumorigenesis and metastasis of various malignancies. However, the role of m6A in pancreatic cancer is still unclear. Exploring genetic alterations and functional networks of m6A regulators in pancreatic cancer may provide new strategies for its treatment. Methods In this study, we used data from the Cancer Genome Atlas (TCGA) database and other public databases through cBioPortal, LinkedOmics, UALCAN, GEPIA, STRING, and the database for annotation, visualization, and integrated discovery (DAVID) to systematically analyze the molecular alterations and functions of 20 main m6A regulators in pancreatic cancer. Results We found that m6A regulators had widespread genetic alterations, and that their expression levels were significantly correlated with pancreatic cancer malignancy. Moreover, m6A regulators were associated with the prognosis of pancreatic cancer patients. Conclusions m6A regulators play a crucial part in the occurrence and development of pancreatic cancer. Our study will guide further studies of m6A RNA modification in pancreatic cancer and could potentially provide new strategies for pancreatic cancer treatment.

scholarly journals MRI Imaging Characteristics of Glioblastoma with Concurrent Gain of Chromosomes 19 and 20

Tomography ◽  
2021 ◽  
Vol 7 (2) ◽  
pp. 228-237
Author(s):  
Taejin L. Min ◽  
Jason W. Allen ◽  
Jose E. Velazquez Vega ◽  
Stewart G. Neill ◽  
Brent D. Weinberg
Keyword(s):  
Methylation Status ◽  
Tumor Location ◽  
Genetic Alterations ◽  
Primary Brain Tumor ◽  
Response To Therapy ◽  
Recent Analysis ◽  
Imaging Features ◽  
Idh Mutation ◽  
Mri Imaging ◽  
Imaging Characteristics

Glioblastoma (GBM) is the most common and deadly primary brain tumor in adults. Some of the genetic variations identified thus far, such as IDH mutation and MGMT promotor methylation, have implications for survival and response to therapy. A recent analysis of long-term GBM survivors showed that concurrent gain of chromosomes 19 and 20 (19/20 co-gain) is a positive prognostic factor that is independent of IDH mutation status. In this study, we retrospectively identified 18 patients with 19/20 co-gain and compared their imaging features to a control cohort without 19/20 co-gain. Imaging features such as tumor location, size, pial invasion, and ependymal extension were examined manually. When compared without further genetic subclassification, both groups showed similar imaging features except for rates of pial invasion. When each group was subclassified by MGMT promotor methylation status however, the two groups showed different imaging features in a number of additional ways including tumor location, size, and ependymal extension. Our results indicate that different permutations of various genetic mutations that coexist in GBM may interact in unpredictable ways to affect imaging appearance, and that imaging prognostication may be better approached in the context of the global genomic profile rather than individual genetic alterations.

scholarly journals PATH-66. THE GENOMIC LANDSCAPE OF SPINAL CORD EPENDYMOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi158-vi158
Author(s):  
Biswarathan Ramani ◽  
Javier Villanueva-Meyer ◽  
Christine Glastonbury ◽  
Ece Meram ◽  
Kyle Walsh ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Progression Free Survival ◽  
Suppressor Gene ◽  
Tumor Location ◽  
Genetic Alterations ◽  
Lumbar Spinal Cord ◽  
Small Subset ◽  
Mycn Amplification ◽  
Chromosome 22Q ◽  
Significant Difference

Abstract INTRODUCTION Ependymomas are seen throughout the neural axis but spinal cord is most common in adults. A subset arises in the setting of neurofibromatosis 2, whereas most are sporadic, potentially with somatic NF2 inactivation. The genetic drivers in NF2 wildtype tumors are unknown, as is the spectrum of cooperating genetic alterations. METHODS We performed targeted next-generation sequencing (NGS) to assess mutations, rearrangements, and chromosomal copy number alterations in 46 adult spinal cord ependymomas. RESULTS The 24 females and 22 males ranged from 20–73 (median 46) years of age. Tumors were in the cervical (n=24), thoracic (n=12), and lumbar (n=10) spinal cord. Nine tumors (20%) harbored truncating NF2 mutations with loss of the remaining wildtype allele, with frequent monosomy 13q. Thirteen NF2-wildtype tumors (28%) showed monosomy 22q with frequent monosomy 13q and trisomy 7, 9, and 12. Seventeen tumors (37%) carried a near-tetraploid genome, likely due to genomic reduplication with frequent preservation of diploidy in chromosomes 13q (77%), 14q (88%), 21q (53%) and 22q (65%). Remaining cases did not show a recurrent pattern, but one harbored focal high-level MYCN amplification. Three of the six recurrences were seen in the last subgroup; however, there was no significant difference for progression-free survival between four subgroups. None of the NF2-mutant tumors were in lumbar spinal cord, but there was no difference for tumor location or patient age between four subgroups. DISCUSSION Biallelic NF2 mutational inactivation characterizes only a subset of spinal cord ependymomas, and MYCN amplification is likely a genetic driver in a small subset of NF2 wildtype cases. The high frequency of chromosome 22q loss even in NF2-wildtype tumors raises the possibility of cryptic alterations in the NF2 gene not detected by our panel, or perhaps implicates the presence of another as yet unidentified tumor suppressor gene on chromosome 22q.

scholarly journals MEGF10, a Glioma Survival-Associated Molecular Signature, Predicts IDH Mutation Status

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Guanzhang Li ◽  
Zhiliang Wang ◽  
Chuanbao Zhang ◽  
Xing Liu ◽  
Fuqiang Yang ◽  
...  
Keyword(s):  
Promoter Region ◽  
Genetic Alterations ◽  
Primary Brain Tumor ◽  
The Cancer Genome Atlas ◽  
Molecular Signature ◽  
Common Mutation ◽  
Lower Grade ◽  
Idh Mutation ◽  
Mutation Status ◽  
Genome Atlas

Glioma is the most common primary brain tumor with various genetic alterations; among which, IDH mutation is the most common mutation and plays an important role in glioma early development, especially in lower grade glioma (LGG, WHO II-III). Previous studies have found that IDH mutation is tightly associated with extensive methylation across whole genome in glioma. To further investigate the role of IDH, we obtained methylation data of 777 samples from CGGA (Chinese Glioma Genome Atlas) and TCGA (The Cancer Genome Atlas) with IDH mutation status available. A package compiled under R language called Tspair was used as the main analytic tool to find potential probes that were significantly affected by IDH mutation. As a result, we found one pair of probes, cg06940792 and cg26025891, which was capable of predicting IDH mutation status precisely. The hypermethylated probe was cg06940792, designed in the promoter region of MEGF10, while the hypomethylated probe was cg26025891, designed in the promoter region of PSTPIP1. Survival analysis proved that hypermethylation or low expression of MEGF10 indicated a favorable prognosis in 983 glioma samples. Moreover, gene ontology analysis demonstrated that MEGF10 was associated with cell migration, cell proliferation, and regulation of apoptosis in glioma. All findings above can be validated in three other independent cohorts. In a word, our results suggested that methylation level and mRNA expression of MEGF10 in glioma were not only correlated with IDH mutation but also associated with clinical outcome of patients, providing potential guide for future dissection of IDH role in glioma.

Multiple genetic alterations to predict the clinical outcome for bevacizumab plus chemotherapy in advanced ovarian cancer: A retrospective study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17037-e17037
Author(s):  
Nan Du ◽  
Jie Gao ◽  
Fang Li ◽  
Zihao Liu ◽  
Huoming Chen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cox Regression ◽  
Target Therapy ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Genetic Alterations ◽  
The Cancer Genome Atlas ◽  
P Value ◽  
Positive Trend ◽  
Wild Type

e17037 Background: Bevacizumab(BV) plus chemotherapy is widely used in patients with advanced ovarian cancer(OC). However, there was not predict biomakers to determined the use of BV-based treatment in OC currently.Therefore, exploring the predict biomarkers for BV is imperative. Methods: Tumor issues of advanced OC treated with BV plus chemotherapy were used for next generation sequencing (NGS) with a 150-gene targeted panel. The correlation between Progression-Free Survival (PFS) and genes or clinicopathology features was analyzed by Kaplan-Meier or Cox regression. For multivariate Cox regression, all factors with a p-value < 0.05 in univariate Cox regression were included. The potential predictive genes would be analyzed with VEGF-related signatures by using 374 OC mRNA data from The Cancer Genome Atlas (TCGA).Statistical analysis was performed using GraphPad Prism and SPSS. Results: 62 Chinese advanced OC patients treated with BV-base therapy were enrolled in this study from May 2015 to March 2018.The median PFS of these patients was 5.7 months , while ORR and DCR rate was 14.5% and 96.8%, repecitively.Patients with EGFR or HER2 alterations had poorer PFS compared with wild-type (EGFR,4.2 months vs. 7.4 months,p = 0.019;HER2,3.8 months vs. 7.3 months, p = 0.045), while MYC amplification patients got better PFS than MYC wild-type patients(17.4 months vs. 6.0 months,p = 0.049). However, in multivariate Cox regression anlysis, EGFR and HER2 were significantly correlated with PFS(P < 0.001 and p = 0.016,respectively),and MYC amplification seemed to have a positive trend(p = 0.052).Moreover,patients with HER2 alterations has a poorer OS(p = 0.008).The VEGF-related signatures analysis results indicated EGFR variants may upregulated VEGFA expression to induced resistant of BV,while downregulation of HIF was significantly correlated with MYC amplification,which was beneficial to efficacy of BV.HER2 alterations has not correlated with VEGF pathways,suggesting HER2 was a poor prognosis of OC instead of an negative predictor of BV. Conclusions: NGS is an effective method to reveal the potential predictor for BV plus chemotherapy in advanced ovarian cancer, and the patients with EGFR or HER2 alterations should consider alternative regimens such as anti-EGFR or anti-HER2 target therapy instead of BV-based regimens.

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