Abstract 427: A path towards determining tumor mutation burden and identifying neoantigens using next-generation sequencing (NGS)

2017 ◽  
Author(s):  
Alex So ◽  
Shannon Kaplan ◽  
Nai-yu Wang ◽  
Shile Zhang ◽  
Aaron Wise ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Next Generation ◽  
Tumor Mutation Burden ◽  
Mutation Burden ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Two Components of Variant Profiles in Primary Vaginal Carcinosarcoma via Next-Generation Sequencing and a Literature Review

2021 ◽  
pp. 106689692110379
Author(s):  
Rakan Kotoku ◽  
Shintaro Yanazume ◽  
Takafumi Kuroda ◽  
Yusuke Kobayashi ◽  
Ikumi Kitazono ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Vaginal Bleeding ◽  
Surgical Excision ◽  
Next Generation ◽  
Tumor Mutation Burden ◽  
Mutation Burden ◽  
Aggressive Tumor ◽  
Post Menopausal ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Primary vaginal carcinosarcoma (VCS) is an extremely rare and aggressive tumor consisting of admixed malignant epithelial and mesenchymal elements. We report a case of VCS that was subjected to analysis by immunohistochemistry and next-generation sequencing (NGS). A 53-year-old woman with post-menopausal vaginal bleeding underwent surgical excision followed by concurrent chemoradiation. A well demarcated tumor was growing in a discontinuous fashion at a location some distance from both the cervix and vulva. Microscopically, the tumor consisted of adenocarcinoma components and sarcoma components consisting of a sheet-like growth of spindle-shaped cells, and we diagnosed this tumor as primary vaginal carcinosarcoma. NGS analysis of each component identified the following variants, TP53, PIK3CA, KRAS and FBXW7. A comparison of microsatellite instability (MSI) and tumor mutation burden (TMB) showed that within both tissues the sarcomatous components had a higher MSI and TMB than the carcinomatous components. This case supports “a monoclonal theory” with the genome profile being similar to other malignant mixed Müllerian tumors.

Tumor Mutation Burden Computation in Two Pan-Cancer Precision Medicine Next-Generation Sequencing Panels

2020 ◽  
Vol 27 (10) ◽  
pp. 1553-1560 ◽  
Author(s):  
Yongqian Shu ◽  
Xiaohong Wu ◽  
Jia Shen ◽  
Dongdong Luo ◽  
Xiang Li ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Precision Medicine ◽  
Next Generation ◽  
Tumor Mutation Burden ◽  
Mutation Burden ◽  
Pan Cancer ◽  
Generation Sequencing

scholarly journals Analysis of MDM2 Amplification: Next-Generation Sequencing of Patients With Diverse Malignancies

2018 ◽  
pp. 1-14 ◽  
Author(s):  
Shumei Kato ◽  
Jeffrey S. Ross ◽  
Laurie Gay ◽  
Farshid Dayyani ◽  
Jason Roszik ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Mapk Signaling ◽  
Small Subset ◽  
Next Generation ◽  
Investigational Agent ◽  
Mutation Burden ◽  
Tumor Types ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing ◽  
Mdm2 Amplification

Purpose MDM2 amplification can promote tumorigenesis directly or indirectly through p53 inhibition. MDM2 has increasing clinical relevance because inhibitors are under evaluation in clinical trials, and MDM2 amplification is a possible genomic correlate of accelerated progression, known as hyperprogression, after anti–PD-1/PD-L1 immunotherapy. We used next-generation sequencing (NGS) to ascertain MDM2 amplification status across a large number of diverse cancers. Methods We interrogated the molecular profiles of 102,878 patients with diverse malignancies for MDM2 amplification and co-altered genes using clinical-grade NGS (182 to 465 genes). Results MDM2 amplification occurred in 3.5% of patients (3,650 of 102,878). The majority of tumor types had a small subset of patients with MDM2 amplification. Most of these patients (99.0% [3,613/3,650]) had co-alterations that accompanied MDM2 amplification. Various pathways, including those related to tyrosine kinase (37.9% [1,385 of 3,650]), PI3K signaling (25.4% [926 of 3,650]), TP53 (24.9% [910 of 3,650]), and MAPK signaling (23.6% [863 of 3,650]), were involved. Although infrequent, mismatch repair genes and PD-L1 amplification also were co-altered (2.2% [79 of 3,650]). Most patients (97.6% [3,563 of 3,650]) had one or more co-alterations potentially targetable with either a Food and Drug Administration–approved or investigational agent. MDM2 amplifications were less frequently associated with high tumor mutation burden compared with the MDM2 wild-type population (2.9% v 6.5%; P < .001). An illustrative patient who harbored MDM2 amplification and experienced hyperprogression with an immune checkpoint inhibitor is presented. Conclusion MDM2 amplification was found in 3.5% of 102,878 patients, 97.6% of whom harbored genomic co-alterations that were potentially targetable. This study suggests that a small subset of most tumor types have MDM2 amplification as well as pharmacologically tractable co-alterations.

scholarly journals Prognostic Factors of Non-Muscle Invasive Bladder Cancer: A Study Based on Next-generation Sequencing

2020 ◽  
Author(s):  
Yanxiang Shao ◽  
Xu Hu ◽  
Zhen Yang ◽  
Thongher Lia ◽  
Weixiao Yang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Prognostic Factors ◽  
Next Generation Sequencing ◽  
Invasive Bladder Cancer ◽  
Next Generation ◽  
Muscle Invasive Bladder Cancer ◽  
Tumor Mutation Burden ◽  
Mutation Burden ◽  
Muscle Invasive ◽  
Generation Sequencing

Abstract ObjectiveTo investigate the genetic prognostic factors for the recurrence of non-muscle invasive bladder cancer. Materials and MethodsThe patients underwent transurethral resection of bladder tumor and received bacillus Calmette–Guérin (BCG) or epirubicin. Next-generation sequencing was performed and alterations of genes, pathways, and tumor mutation burden were recorded. Associations between these clinicopathological and genetic variants were estimated, and prognostic factor identified.ResultsA total of 58 cases were included in our study, and 46 patients underwent treatment with BCG. FGFR3 was the most frequently altered gene (48%), and more commonly detected in intermediate-risk patients. Univariate Cox analysis demonstrated that 10 genes were significantly correlated with BCG failure, while NEB, FGFR1 and SDHC were independent recurrence predictors. Besides, epigenetic-related gene pathway mutations were negatively correlated with recurrence (hazard ratio: 0.198, P=0.023). DNA damage response and repair gene alterations were positively correlated with tumor burden, while altered TP53 was most frequent among these genes and significant correlated with high tumor burden.ConclusionBCG instillation significantly reduced the rate of recurrence compared with epirubicin in this population. Potential biomarkers and therapeutic targets were found with the help of next-generation sequencing; correlations between DDR genes alterations and high tumor mutation burden were also demonstrated.

scholarly journals Durable Response to PD-1 Blockade in a Patient With Metastatic Pancreatic Undifferentiated Carcinoma With Osteoclast-Like Giant Cells

2021 ◽  
Vol 19 (3) ◽  
pp. 247-252
Author(s):  
Robert J. Besaw ◽  
Adrienne R. Terra ◽  
Grace L. Malvar ◽  
Tobias R. Chapman ◽  
Lauren M. Hertan ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Giant Cells ◽  
Undifferentiated Carcinoma ◽  
Ductal Adenocarcinoma ◽  
Next Generation ◽  
Durable Response ◽  
Tumor Mutation Burden ◽  
Mutation Burden ◽  
Generation Sequencing

Undifferentiated carcinoma with osteoclast-like giant cells (UCOGC) of the pancreas is a rare and potentially aggressive variant of pancreatic ductal adenocarcinoma. Data on this disease are sparse, and despite genetic similarities to pancreatic ductal adenocarcinoma, UCOGC clinical outcomes can be markedly different. We report on a female patient aged 62 years who presented with UCOGC with pulmonary metastases initially treated with 2 lines of cytotoxic chemotherapy. After rapid disease progression with both cytotoxic treatments, the patient’s tissue was sent for next-generation sequencing, which revealed a high tumor mutation burden (32 mutations per megabase), as well as somatic mutations in BRAF, NF1, PIK3CA, CDKN2A, TERT, and TP53. Pancreatic cancers have previously demonstrated suboptimal responses to immunotherapeutic approaches. However, given the high tumor mutation burden and distinctiveness of the tumor class, the patient began third-line pembrolizumab monotherapy after palliative radiation to the rapidly progressing and painful abdominal mass from her primary tumor. She had a marked response in her primary UCOGC tumor and metastatic sites, and she remains on pembrolizumab monotherapy with ongoing response after 32 months of therapy. Recent evidence showing significant PD-L1 enrichment on neoplastic cells of undifferentiated carcinomas (including UCOGC) may indicate a role for immunotherapeutic approaches in these patients. Rare cancers such as UCOGC and other undifferentiated carcinomas may benefit from next-generation sequencing to inform treatment decisions when standards of care are absent, as in this report.

Sign in / Sign up

Export Citation Format

Share Document