Data on somatic mutations obtained by whole exome sequencing of FFPE tissue samples from Russian patients with prostate cancer

AbstractInflammatory breast cancer (IBC) is the most aggressive form of breast cancer. Although it is a rare subtype, IBC is responsible for roughly 10% of breast cancer deaths. In order to obtain a better understanding of the genomic landscape and intratumor heterogeneity (ITH) in IBC, we conducted whole-exome sequencing of 16 tissue samples (12 tumor and four normal samples) from six hormone-receptor-positive IBC patients, analyzed somatic mutations and copy number aberrations, and inferred subclonal structures to demonstrate ITH. Our results showed that KMT2C was the most frequently mutated gene (42%, 5/12 samples), followed by HECTD1, LAMA3, FLG2, UGT2B4, STK33, BRCA2, ACP4, PIK3CA, and DNAH8 (all nine genes tied at 33% frequency, 4/12 samples). Our data indicated that PTEN and FBXW7 mutations may be considered driver gene mutations for IBC. We identified various subclonal structures and different levels of ITH between IBC patients, and mutations in the genes EIF4G3, IL12RB2, and PDE4B may potentially generate ITH in IBC.

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Integrative Exome Sequencing Analysis in Castration-Resistant Prostate Cancer in Chinese Population

Current Pharmaceutical Biotechnology ◽

10.2174/1389201019666191003142119 ◽

2020 ◽

Vol 21 (2) ◽

pp. 140-148

Author(s):

Lifang Hao ◽

Hui Li ◽

Su Zhang ◽

Yanlei Yang ◽

Zhenzhen Xu ◽

...

Keyword(s):

Prostate Cancer ◽

Exome Sequencing ◽

Molecular Mechanism ◽

Whole Exome Sequencing ◽

Ffpe Tissue ◽

Sequencing Analysis ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

Phosphorylation Level ◽

Whole Exome

Background: Castration-resistant Prostate Cancer (CRPC) is a fatal disease with rapid growth. The malignancy usually presents with metastasis and poor prognosis, and causes 100% mortality. Therefore, the treatment of CRPC is extremely challenging, and its pathogenesis need to be elucidated urgently. Objective: The high throughput sequencing technology was used to sequence the whole exome associated with CRPC, to explore the molecular mechanism of CRPC, and to find the potential therapeutic targets. Methods: We performed whole-exome sequencing of FFPE tissue from 11 Chinese adult male patients. Genomic DNA was fragmented and enriched for whole-exome sequencing using the QiAamp DNA FFPE Tissue KIT, sequenced on an Illumina HiSeq2000 platform, and the relevant genes were analyzed using biological information. Finally, immunohistochemistry method was used to detect the phosphorylation level of LATS1 in CRPC tissues of MST1 mutant and non-mutant patients. Results: We have screened 85 significant mutant genes with relatively high mutation rates of TP53, AR, KMT2, DMAPK1, PIK3R1, SH2B3, WHSC1, KMT2D, MST1 and MAPK1. We first found that MST1 has multiple mutations in CRPC patients, and the MST1 plays an important role in the Hippo pathway. Immunohistochemistry results showed that the phosphorylation level of LATS1 in the mutant patients was significantly lower than that in the non-mutant patients. Conclusion: We speculate that MST1 would be a new potential target for the treatment of CRPC by regulating Hippo signaling pathway. The results provided an important clue to the molecular mechanism of CRPC.

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Germline and somatic mutations in the pathology of pineal cyst: A whole‐exome sequencing study of 93 individuals

Molecular Genetics & Genomic Medicine ◽

10.1002/mgg3.1691 ◽

2021 ◽

Author(s):

Yuanqing Yan ◽

Rebecca Martinez ◽

Maria N. Rasheed ◽

Joshua Cahal ◽

Zhen Xu ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Somatic Mutations ◽

Pineal Cyst ◽

Whole Exome

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Whole-exome sequencing reveals potential germline and somatic mutations in 60 malignant ovarian germ cell tumors

Biology of Reproduction ◽

10.1093/biolre/ioab052 ◽

2021 ◽

Author(s):

Juan Chen ◽

Yan Li ◽

Jianlei Wu ◽

Yakun Liu ◽

Shan Kang

Keyword(s):

Germ Cell ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Peripheral Blood ◽

Copy Number ◽

Somatic Mutations ◽

Germ Cell Tumors ◽

Germline Mutations ◽

Deletion Region ◽

Whole Exome

Abstract Background Malignant ovarian germ cell tumors (MOGCTs) are rare and heterogeneous ovary tumors. We aimed to identify potential germline mutations and somatic mutations in MOGCTs by whole-exome sequencing. Methods The peripheral blood and tumor samples from these patients were used to identify germline mutations and somatic mutations, respectively. For those genes corresponding to copy number alterations (CNA) deletion and duplication region, functional annotation of was performed. Immunohistochemistry was performed to evaluate the expression of mutated genes corresponding to CNA deletion region. Results In peripheral blood, copy number loss and gain were mostly found in yolk sac tumors (YST). Moreover, POU5F1 was the most significant mutated gene with mutation frequency > 10% in both CNA deletion and duplication region. In addition, strong cytoplasm staining of POU5F1 (corresponding to CNA deletion region) was found in 2 YST and nuclear staining in 2 dysgerminomas (DG) tumor samples. Genes corresponding to CNA deletion region were significantly enriched in the signaling pathway of regulating pluripotency of stem cells. In addition, genes corresponding to CNA duplication region were significantly enriched in the signaling pathways of RIG-I-like receptor, Toll-like receptor, NF-kappa B and Jak–STAT. KRT4, RPL14, PCSK6, PABPC3 and SARM1 mutations were detected in both peripheral blood and tumor samples. Conclusions Identification of potential germline mutations and somatic mutations in MOGCTs may provide a new field in understanding the genetic feature of the rare biological tumor type in the ovary.

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Whole-Exome Sequencing Identifies Somatic Mutations Associated With Mortality in Metastatic Clear Cell Kidney Carcinoma

Frontiers in Genetics ◽

10.3389/fgene.2019.00439 ◽

2019 ◽

Vol 10 ◽

Cited By ~ 3

Author(s):

Alejandro Mendoza-Alvarez ◽

Beatriz Guillen-Guio ◽

Adrian Baez-Ortega ◽

Carolina Hernandez-Perez ◽

Sita Lakhwani-Lakhwani ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Somatic Mutations ◽

Clear Cell ◽

Kidney Carcinoma ◽

Whole Exome

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TP53 and PTEN mutations were shared in concurrent germ cell tumor and acute megakaryoblastic leukemia

BMC Cancer ◽

10.1186/s12885-019-6497-0 ◽

2020 ◽

Vol 20 (1) ◽

Cited By ~ 2

Author(s):

Keiichi Akizuki ◽

Masaaki Sekine ◽

Yasunori Kogure ◽

Takuro Kameda ◽

Kotaro Shide ◽

...

Keyword(s):

Germ Cell ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Germ Cell Tumor ◽

Somatic Mutations ◽

Cell Tumor ◽

Sequencing Analysis ◽

Male Adult ◽

Clonal Relationship ◽

Whole Exome

Abstract Background The occurrence of a mediastinal germ cell tumor (GCT) and hematological malignancy in the same patient is very rare. Due to its rarity, there have been only two reports of the concurrent cases undergoing detailed genetic analysis with whole-exome sequencing (WES), and the possible clonal relationship between the both tumors remained not fully elucidated. Methods We performed whole-exome sequencing analysis of mediastinal GCT and acute myeloid leukemia (AML) samples obtained from one young Japanese male adult patient with concurrent both tumors, and investigated the possible clonal relationship between them. Results Sixteen somatic mutations were detected in the mediastinal GCT sample and 18 somatic mutations in the AML sample. Mutations in nine genes, including TP53 and PTEN both known as tumor suppressor genes, were shared in both tumors. Conclusions All in our case and in the previous two cases with concurrent mediastinal GCT and AML undergoing with whole-exome sequencing analysis, TP53 and PTEN mutations were commonly shared in both tumors. These data not only suggest that these tumors share a common founding clone, but also indicate that associated mediastinal GCT and AML harboring TP53 and PTEN mutations represent a unique biological entity.

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PATH-06. ASSESSMENT OF CIRCULATING TUMOR DNA IN CEREBROSPINAL FLUID BY WHOLE EXOME SEQUENCING TO DETECT GENOMIC ALTERATIONS OF GLIOBLASTOMA

Neuro-Oncology ◽

10.1093/neuonc/noaa215.688 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii165-ii165

Author(s):

Hao Duan ◽

Zhenqiang He ◽

Zhenghe Chen ◽

Yonggao Mou

Keyword(s):

Cerebrospinal Fluid ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Tumor Tissue ◽

Circulating Tumor Dna ◽

Genomic Alterations ◽

Tissue Samples ◽

Whole Exome ◽

Resected Tumor ◽

Tumor Dna

Abstract Cerebrospinal fluid (CSF) has been demonstrated as a better source of circulating tumor DNA (ctDNA) than plasma for brain tumors. However, it is unclear whether whole exome sequencing (WES) is qualified for detection of ctDNA in CSF. The aim of this study was to determine if assessment of ctDNA in CSF by WES is a feasible approach to detect genomic alterations of glioblastoma. CSFs of ten glioblastoma patients were collected pre-operatively at the Department of Neurosurgery, Sun Yat-sen University Cancer Center. ctDNA in CSF and genome DNA in the resected tumor were extracted and subjected to WES. The identified glioblastoma-associated mutations from ctDNA in CSF and genome DNA in the resected tumor were compared. Due to the ctDNA in CSF was unqualified for exome sequencing for one patient, nine patients were included into the final analysis. More glioblastoma-associated mutations tended to be detected in CSF comparing with the corresponding tumor tissue samples (3.56±0.75 vs. 2.22±0.32, P=0.097), while the statistical significance was limited by the small sample size. The average mutation frequencies were similar in CSF and tumor tissue samples (74.12% ± 6.03% vs. 73.83% ± 5.95%, P = 0.924). The R132H mutation of isocitrate dehydrogenase 1 and the G34V mutation of H3F3A which had been reported in the pathological diagnoses were also detected from ctDNA in CSF by WES. Patients who received temozolomide chemotherapy previously or those whose tumor involved subventricular zone tended to harbor more mutations in their CSF. Assessment of ctDNA in CSF by WES is a feasible approach to detect genomic alterations of glioblastoma, which may provide useful information for the decision of treatment strategy.

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