scholarly journals Whole-Exome Sequencing of Rare Site Endometriosis-Associated Cancer

Diseases ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 14
Author(s):  
Sonomi Kurose ◽  
Kentaro Nakayama ◽  
Sultana Razia ◽  
Masako Ishikawa ◽  
Tomoka Ishibashi ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Tumor Suppressor Genes ◽  
Undifferentiated Carcinoma ◽  
Small Subset ◽  
Breast Cancers ◽  
Whole Exome ◽  
Rare Site ◽  
Actionable Variants

Malignant transformation of extraovarian endometriosis is rare, with the carcinogenesis mechanism unclear. To clarify the actionable variants of rare-site endometriosis-associated cancer (RSEAC), we performed whole-exome sequencing for the tumor, in two patients. The intestine was affected in both cases, although the histology was that of clear cell carcinoma and undifferentiated carcinoma, respectively. Therefore, the cases were referred to as endometriosis-associated intestinal tumors (EIATs). Actionable variants (all frameshift mutations) were identified in tumor suppressor genes ARID1A, PTEN, and p53; however, no oncogenic variants were identified. Both cases were microsatellite stable. The patient with undifferentiated carcinoma exhibited hypermutator and homologous recombination deficiency phenotypes. The dominant mutation signatures were signature 30 (small subset of breast cancers) and 19 (pilocytic astrocytoma) in patient 1, and signature 5 (small subset of breast cancers) and 3 (breast, ovarian, and pancreatic cancers) in patient 2. Immunohistochemistry revealed positive CD8 and PD-1 expression in both patients; patient 1 also showed positive PDL-1 expression. Our results suggest that RSEAC is associated with variants of tumor suppressor genes as epigenetic alterations. Mutation signature-based whole-exome sequencing could be useful to select an adjuvant chemotherapy regimen. High CD8 and PD-1 expression in RSEAC suggests that immune checkpoint inhibitors are useful for treatment.

scholarly journals Centenarian Exomes as a Tool for Evaluating the Clinical Relevance of Germline Tumor Suppressor Mutations

2020 ◽  
Vol 19 ◽  
pp. 153303382091108
Author(s):  
Lubomir Balabanski ◽  
Dimitar Serbezov ◽  
Dragomira Nikolova ◽  
Olga Antonova ◽  
Desislava Nesheva ◽  
...  
Keyword(s):  
Risk Factors ◽  
Tumor Suppressor ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Clinical Relevance ◽  
Tumor Suppressor Genes ◽  
Sequencing Data ◽  
Exome Sequencing Data ◽  
Whole Exome ◽  
Whole Exome Sequencing Data

Objectives: The aim of the present study was to evaluate the clinical relevance of mutations in tumor suppressor genes using whole-exome sequencing data from centenarians and young healthy individuals. Methods: Two pools, one of centenarians and one of young individuals, were constructed and whole-exome sequencing was performed. We examined the whole-exome sequencing data of Bulgarian individuals for carriership of tumor suppressor gene variants. Results: Of all variants annotated in both pools, 5080 (0.06%) are variants in tumor suppressor genes but only 46 show significant difference in allele frequencies between the two studied groups. Four variants (0.004%) are pathogenic/risk factors according to single nucleotide polymorphism database: rs1566734 in PTPRJ, rs861539 in XRCC3, rs203462 in AKAP10, and rs486907 in RNASEL. Discussion: Based on their high minor allele frequencies and presence in the centenarian group, we could reclassify them from pathogenic/risk factors to benign. Our study shows that centenarian exomes can be used for re-evaluating the clinically uncertain variants.

scholarly journals Rare Tumor-Normal Matched Whole Exome Sequencing Identifies Novel Genomic Pathogenic Germline and Somatic Aberrations

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1618
Author(s):  
Ryan Sprissler ◽  
Bryce Perkins ◽  
Laurel Johnstone ◽  
Hani M. Babiker ◽  
Pavani Chalasani ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Tumor Suppressor Genes ◽  
Tumor Type ◽  
Rare Cancer ◽  
Suppressor Genes ◽  
Germline Variants ◽  
Rare Tumors ◽  
Whole Exome

Whole exome sequencing (WES) of matched tumor-normal pairs in rare tumors has the potential to identify genome-wide mutations and copy number alterations (CNAs). We evaluated 27 rare cancer patients with tumor-normal matching by WES and tumor-only next generation sequencing (NGS) as a comparator. Our goal was to: 1) identify known and novel variants and CNAs in rare cancers with comparison to common cancers; 2) examine differences between germline and somatic variants and how that functionally impacts rare tumors; 3) detect and characterize alleles in biologically relevant genes-pathways that may be of clinical importance but not represented in classical cancer genes. We identified 3343 germline single nucleotide variants (SNVs) and small indel variants—1670 in oncogenes and 1673 in tumor suppressor genes—generating an average of 124 germline variants/case. The number of somatic SNVs and small indels detected in all cases was 523:306 in oncogenes and 217 in tumor suppressor genes. Of the germline variants, six were identified to be pathogenic or likely pathogenic. In the 27 analyzed rare cancer cases, CNAs are variable depending on tumor type, germline pathogenic variants are more common. Cell fate pathway mutations (e.g., Hippo, Notch, Wnt) dominate pathogenesis and double hit (mutation + CNV) represent ~18% cases.

scholarly journals Correction: Whole exome sequencing reveals mutations in FAT1 tumor suppressor gene clinically impacting on peripheral T-cell lymphoma not otherwise specified

2019 ◽  
Vol 33 (2) ◽  
pp. 319-319
Author(s):  
Maria Antonella Laginestra ◽  
Luciano Cascione ◽  
Giovanna Motta ◽  
Fabio Fuligni ◽  
Claudio Agostinelli ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Suppressor ◽  
Exome Sequencing ◽  
Tumor Suppressor Gene ◽  
Whole Exome Sequencing ◽  
Cell Lymphoma ◽  
Suppressor Gene ◽  
Peripheral T Cell Lymphoma ◽  
Not Otherwise Specified ◽  
Whole Exome

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

scholarly journals Whole exome sequencing reveals mutations in FAT1 tumor suppressor gene clinically impacting on peripheral T-cell lymphoma not otherwise specified

2019 ◽  
Vol 33 (2) ◽  
pp. 179-187 ◽  
Author(s):  
Maria Antonella Laginestra ◽  
Luciano Cascione ◽  
Giovanna Motta ◽  
Fabio Fuligni ◽  
Claudio Agostinelli ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Suppressor ◽  
Exome Sequencing ◽  
Tumor Suppressor Gene ◽  
Whole Exome Sequencing ◽  
Cell Lymphoma ◽  
Suppressor Gene ◽  
Peripheral T Cell Lymphoma ◽  
Not Otherwise Specified ◽  
Whole Exome

Whole exome sequencing reveals potentially pathogenic variants in a small subset of premenopausal women with idiopathic osteoporosis

Bone ◽  
2021 ◽  
pp. 116253
Author(s):  
Adi Cohen ◽  
Joseph Hostyk ◽  
Evan H. Baugh ◽  
Christie M. Buchovecky ◽  
Vimla S. Aggarwal ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Premenopausal Women ◽  
Small Subset ◽  
Idiopathic Osteoporosis ◽  
Pathogenic Variants ◽  
Whole Exome

scholarly journals Whole-exome sequencing detection of the somatic mutations associated with the tumorigenesis and gefitinib-response of mucoepidermoid carcinomas

2020 ◽  
Author(s):  
Yufeng Wu ◽  
Zhen He ◽  
Zhe Zhang ◽  
Lili Wang ◽  
Sen Yang ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Tumor Suppressor Genes ◽  
Somatic Mutations ◽  
Complete Response ◽  
Synonymous Mutations ◽  
Whole Exome ◽  
Potential Applications ◽  
Gefitinib Treatment ◽  
Mutant Genes

Abstract Background: We performed whole-exome sequencing (WES) on the sputum and blood samples of a MEC patient exploring the genetic alternations underlying the mechanism of mucoepidermoid carcinomas (MEC) and gefitinib response.Methods: We previously reported a 10-year old MEC patient who was cured after a complete response to gefitinib treatment. Whole-exome sequencing (WES) was performed on the samples of this patient to detect somatic mutations. Detected genes harboring somatic mutations were compared with previously reported mutant genes related to MEC.Results: Somatic mutations were detected in 13 previously reported oncogene and tumor suppressors, and enriched in apoptosis (RIPK1, SPTA1, and ACTG1). The loss and gain of phosphorylation amino acids occurred in 8 of the 34 non-synonymous mutations, which resided in ARL6, DNAH11, PGM5, PRAMEF15, RALGAPB, RANBP2, TTN, and UBN1. TTN bared two Ala to Thr mutations. Among the 50 genes containing detected somatic mutations, ADAM28, DYSF, GP2, PPP2R5B, and TTN were also detected in a previous study; and all of these overlaps were identified in low and intermediate grade samples.Conclusions: These findings underline the possibility of the accumulated somatic mutations in the tumor suppressor genes and oncogenes might contribute to the tumorigenesis of our MEC patient, which have potential applications for the therapies of MEC.

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