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Abstract Background Large-scale sequencing plays important roles in revealing the genomic map of ccRCC and predicting prognosis and therapeutic response to targeted drugs. However, the relevant clinical data is still sparse in Chinese population. Methods Fresh tumor specimens were collected from 66 Chinese ccRCC patients, then the genomic RNAs were subjected to whole transcriptome sequencing (WTS). We comprehensively analyzed the frequently mutated genes from our hospital’s cohort as well as TCGA-KIRC cohort. Results VHL gene is the most frequently mutated gene in ccRCC. In our cohort, BAP1 and PTEN are significantly associated with a higher tumor grade and DNM2 is significantly associated with a lower tumor grade. The mutant type (MT) groups of BAP1 or PTEN, BAP1 or SETD2, BAP1 or TP53, BAP1 or MTOR, BAP1 or FAT1 and BAP1 or AR had a significantly correlation with higher tumor grade in our cohort. Moreover, we identified HMCN1 was a hub mutant gene which was closely related to worse prognosis and may enhance anti-tumor immune responses. Conclusions In this preliminary research, we comprehensively analyzed the frequently mutated genes in the Chinese population and TCGA database, which may bring new insights to the diagnosis and medical treatment of ccRCC.

Background: Large-scale sequencing plays important roles in revealing the genomic map of ccRCC and predicting prognosis and therapeutic response to targeted drugs. However, the relevant clinical data is still sparse in Chinese population. Methods: Fresh tumor specimens were collected from 66 Chinese ccRCC patients, then the genomic RNAs were subjected to whole transcriptome sequencing (WTS). We comprehensively analyzed the frequently mutated genes from our hospital's cohort as well as TCGA-KIRC cohort. Results: VHL gene is the most frequently mutated gene in ccRCC. In our cohort, BAP1 and PTEN are significantly associated with a higher tumor grade and DNM2 is significantly associated with a lower tumor grade. The mutant type (MT) groups of BAP1 or PTEN, BAP1 or SETD2, BAP1 or TP53, BAP1 or MTOR, BAP1 or FAT1 and BAP1 or AR had a significantly correlation with higher tumor grade in our cohort. Moreover, we identified HMCN1 was a hub mutant gene which was closely related to worse prognosis and may enhance anti-tumor immune responses. Conclusions: In this preliminary research, we comprehensively analyzed the frequently mutated genes in the Chinese population and TCGA database, which may bring new insights to the diagnosis and medical treatment of ccRCC. [ABSTRACT FROM AUTHOR]

Abstract Background Pancreatic Ductal Adenocarcinoma (PDAC) is a cancer of the exocrine pancreas and 5-year survival rates remain constant at 7%. Along with PDAC, Periampullary Adenocarcinoma (PAC) accounts for 0.5–2% of all gastrointestinal malignancies. Genomic observations were well concluded for PDAC and PACs in western countries but no reports are available from India till now. Methods Targeted Next Generation Sequencing were performed in 8 (5 PDAC and 3 PAC) tumour normal pairs, using a panel of 412 cancer related genes. Primary findings were replicated in 85 tumour samples (31 PDAC and 54 PAC) using the Sanger sequencing. Mutations were also validated by ASPCR, RFLP, and Ion Torrent sequencing. IHC along with molecular dynamics and docking studies were performed for the p.A138V mutant of TP53. Key polymorphisms at TP53 and its associated genes were genotyped by PCR-RFLP method and association with somatic mutations were evaluated. All survival analysis was done using the Kaplan-Meier survival method which revealed that the survival rates varied significantly depending on the somatic mutations the patients harboured. Results Among the total 114 detected somatic mutations, TP53 was the most frequently mutated (41%) gene, followed by KRAS, SMAD4, CTNNB1, and ERBB3. We identified a novel hotspot TP53 mutation (p.A138V, in 17% of all patients). Low frequency of KRAS mutation (33%) was detected in these samples compared to patients from Western counties. Molecular Dynamics (MD) simulation and DNA-protein docking analysis predicted p.A138V to have oncogenic characteristics. Patients with p.A138V mutation showed poorer overall survival (p = 0.01). So, our finding highlights elevated prevalence of the p53p.A138V somatic mutation in PDAC and pancreatobiliary PAC patients. Conclusion Detection of p.A138V somatic variant in TP53 might serve as a prognostic marker to classify patients. It might also have a role in determining treatment regimes. In addition, low frequency of KRAS hotspot mutation mostly in Indian PDAC patient cohort indicates presence of other early drivers in malignant transformation.

Spinal schwannoma is the most common primary spinal tumor but its genomic landscape and underlying mechanism driving its initiation remain elusive. The aim of the present study was to gain further insights into the molecular mechanisms of this kind of tumor through whole genome sequencing of nine spinal schwannomas and paired blood samples. The results showed that ATM, CHD4, FAT1, KMT2D, MED12, NF2, and SUFU were the most frequently mutated cancer-related genes. In addition, the somatic copy number alterations (CNA) was potentially associated with spinal schwannoma, among which NF2 was found to be frequently deleted in schwannoma samples. Only a few genes were located within the amplified regions. In contrast, the deleted regions in 15q15.1 and 7q36.1 contained most of these genes. With respect to tumorigenesis, NF2 had the highest variant allele frequency (VAF) than other genes, and homozygous deletion was observed in NF1, NF2, and CDKN2C. Pathway-level analysis suggested that Hippo signaling pathway may be a critical pathway controlling the initiation of spinal schwannoma. Collectively, this systematic analysis of DNA sequencing data revealed that some key genes including NF1, NF2, and CDKN2C and Hippo signaling pathway were associated with spinal schwannoma, which may help improve our understanding about the genomic landscape of spinal schwannoma.

Spinal schwannoma is the most common primary spinal tumor but its genomic landscape and underlying mechanism driving its initiation remain elusive. The aim of the present study was to gain further insights into the molecular mechanisms of this kind of tumor through whole genome sequencing of nine spinal schwannomas and paired blood samples. The results showed that ATM, CHD4, FAT1, KMT2D, MED12, NF2 , and SUFU were the most frequently mutated cancer-related genes. In addition, the somatic copy number alterations (CNA) was potentially associated with spinal schwannoma, among which NF2 was found to be frequently deleted in schwannoma samples. Only a few genes were located within the amplified regions. In contrast, the deleted regions in 15q15.1 and 7q36.1 contained most of these genes. With respect to tumorigenesis, NF2 had the highest variant allele frequency (VAF) than other genes, and homozygous deletion was observed in NF1 , NF2 , and CDKN2C. Pathway-level analysis suggested that Hippo signaling pathway may be a critical pathway controlling the initiation of spinal schwannoma. Collectively, this systematic analysis of DNA sequencing data revealed that some key genes including NF1 , NF2 , and CDKN2C and Hippo signaling pathway were associated with spinal schwannoma, which may help improve our understanding about the genomic landscape of spinal schwannoma. [ABSTRACT FROM AUTHOR]

Background: Pancreatic Ductal Adenocarcinoma (PDAC) is a cancer of the exocrine pancreas and 5-year survival rates remain constant at 7%. Along with PDAC, Periampullary Adenocarcinoma (PAC) accounts for 0.5–2% of all gastrointestinal malignancies. Genomic observations were well concluded for PDAC and PACs in western countries but no reports are available from India till now. Methods: Targeted Next Generation Sequencing were performed in 8 (5 PDAC and 3 PAC) tumour normal pairs, using a panel of 412 cancer related genes. Primary findings were replicated in 85 tumour samples (31 PDAC and 54 PAC) using the Sanger sequencing. Mutations were also validated by ASPCR, RFLP, and Ion Torrent sequencing. IHC along with molecular dynamics and docking studies were performed for the p.A138V mutant of TP53. Key polymorphisms at TP53 and its associated genes were genotyped by PCR-RFLP method and association with somatic mutations were evaluated. All survival analysis was done using the Kaplan-Meier survival method which revealed that the survival rates varied significantly depending on the somatic mutations the patients harboured. Results: Among the total 114 detected somatic mutations, TP53 was the most frequently mutated (41%) gene, followed by KRAS, SMAD4, CTNNB1, and ERBB3. We identified a novel hotspot TP53 mutation (p.A138V, in 17% of all patients). Low frequency of KRAS mutation (33%) was detected in these samples compared to patients from Western counties. Molecular Dynamics (MD) simulation and DNA-protein docking analysis predicted p.A138V to have oncogenic characteristics. Patients with p.A138V mutation showed poorer overall survival (p = 0.01). So, our finding highlights elevated prevalence of the p53p.A138V somatic mutation in PDAC and pancreatobiliary PAC patients. Conclusion: Detection of p.A138V somatic variant in TP53 might serve as a prognostic marker to classify patients. It might also have a role in determining treatment regimes. In addition, low frequency of KRAS hotspot mutation mostly in Indian PDAC patient cohort indicates presence of other early drivers in malignant transformation. [ABSTRACT FROM AUTHOR]