scholarly journals Identification of somatic genetic alterations in ovarian clear cell carcinoma with next generation sequencing

2017 ◽  
Vol 57 (2) ◽  
pp. 51-60 ◽  
Author(s):  
Yusuke Shibuya ◽  
Hideki Tokunaga ◽  
Sakae Saito ◽  
Kazurou Shimokawa ◽  
Fumiki Katsuoka ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Genetic Alterations ◽  
Next Generation ◽  
Ovarian Clear Cell Carcinoma ◽  
Generation Sequencing

Prognostic and predictive biomarkers for clear cell renal cell carcinoma utilizing next generation sequencing.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16070-e16070
Author(s):  
Jamal Zekri ◽  
Abdelrazak Meliti ◽  
Mohammed Abhas Baghdadi ◽  
Turki Sobahy ◽  
Saba Imtiaz
Keyword(s):  
Renal Cell Carcinoma ◽  
Next Generation Sequencing ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Predictive Biomarkers ◽  
High Potential ◽  
Next Generation ◽  
Cell Renal Cell Carcinoma ◽  
Generation Sequencing

e16070 Background: The management of the clear cell renal cell carcinoma (cc-RCC) has evolved over the past decade. Clinical patients’ and tumor characteristics have a limited role in predicting the outcome of these patients. The search for reliable prognostic and predictive biomarkers should be pursued in particular during the current era of next generation sequencing (NGS) technology. Methods: Formalin-Fixed Paraffin-Embedded (FFPE) tissue specimens of cc-RCC were sequenced using NGS and a customized gene panel testing for 72 tumor-related genes. High potential variants were defined by mutation effect (stop-loss, stop-gain, frame-shift substitutions or non-synonymous SNV) and class (pathogenic or likely pathogenic). Cases with identical variants were identified. Results: In total, all 47 cases had 69,052 variants, of which 20,453 were classified as high potential variants. Identical alterations in 15 genes were present in all samples. These genes are: MUC3A, MUC12, MUC7, SRRT, MUC2, MUC5AC, MUC5B, MUC22, MUC6, CR1, MUC4, MUC16, MUC19, MUC17 and MERTK. The numbers of identical and non-identical variants in these 15 genes were counted for each sample. Median number of variants was 377 and was selected as a cut off to define cases with high ( > 377) and low (≤377) variants number (HVN and LVN respectively). For the whole cohort, HVN was associated with shorter overall survival compared to LVN (Median 50 months vs. not reached; Log Rank P = 0.041). In the 11 patients who received anti-angiogenic tyrosine kinase inhibitors (TKIs), HVN was associated with a trend of shorter progression free survival (Median 5 vs. 10 months; Log Rank P = not significant). Conclusions: Alterations in SRRT, CR1, MERTK and MUCIN family genes are very common in RCC. HVN ( > 377) is associated with worse prognosis and may predict decreased benefit from anti-angiogenic TKIs.

Integrative genomic and transcriptomic analysis reveals prognostic markers and immune subtype in Chinese ovarian clear cell carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17529-e17529
Author(s):  
Huijuan Yang ◽  
Shuang Ye ◽  
Qin Li ◽  
Yutuan Wu ◽  
Wei Jiang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Carcinoma ◽  
Prognostic Markers ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Genetic Alterations ◽  
Transcriptomic Analysis ◽  
Clinical Factors ◽  
Ovarian Clear Cell Carcinoma ◽  
Poor Survival

e17529 Background: Ovarian clear cell carcinoma (OCCC) is a subtype of ovarian cancer characterized by chemo-resistance and poor survival. Herein, we performed comprehensive genomic and transcriptomic profiling of OCCC tissues to identify prognostic markers and immune subtype in Chinese patients. Methods: A total of 61 patients were included, comprising 41 early-stage and 19 late-stage tumors. Tissue samples were collected before chemotherapy and subjected to capture-based targeted sequencing using a panel consisting of 520 cancer related genes and whole transcriptomic sequencing. Genetic alterations, tumor mutation burden (TMB), microsatellite instability (MSI), and gene expression were evaluated. Association analysis was performed to evaluate clinical and genetic factors with platinum-sensitivity and treatment effects. A nomogram was constructed to predict survival outcomes. Single sample Gene Set Enrichment analysis (ssGSEA) was performed with gene expression profile and immune gene sets. Results: Genetic alterations were mainly identified in ARID1A (49%), PIK3CA (48%), TP53 (18%), ATM (15%), SMARCA4 (13%) and PRKDC (13%). Co-occurrence of mutations in ARID1A with PIK3CA and PRKDC were observed (p < 0.05). Meanwhile, no alterations were identified in BRCA1/2. Patients harboring ATM mutations tended to be platinum sensitive compared to those wildtype counterparts (p < 0.05). In patients with stage IV OCCC, mutations of ARID1A, PIK3CA, SMARCA4 and the HRR pathway were also related to higher percentage of platinum-sensitivity, though significance was not achieved. Mutations of FGFR2, NOTCH1 and the BER pathway were more frequently identified in patients with stage II to IV than stage I (p < 0.05). Patients harboring alterations at chromosome 8q covering genes such as PRKDC showed better overall survival (OS) (p < 0.05). Both clinical factors and frequently mutated genes were used to construct a nomogram for progression-free survival (PFS) prediction. The clinical factors (stage, platinum response and residual disease) in combination with genetic mutations ( ATM and SMARCA4) showed better performance in predicting PFS than clinical factors alone (concordance index 0.85 vs. 0.74, p < 0.01). Transcriptomic analysis with ssGSEA of immune pathway revealed an immune subtype with enrichment of PD-1 signaling. OCCC patients with this immune subtype showed poor PFS and OS. Integration of genomic and transcriptomic analysis showed that the immune subtype patients had higher mutation rate of PIK3CA. Conclusions: The mutational profiles of OCCC were varied in patients with different platinum response and tumor stages. An immune subtype of OCCC with poor survival and enrichment of PD-1 signaling was identified. Our study identified several potential prognostic markers of OCCC at genetic level and revealed an immune subtype for potential immunotherapy.

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