Whole-exome sequencing in a patient with synchronous triple primary malignancies involving lung cancer: a case report

Abstract The incidence of multiple primary malignancies (MPMs) has been increasing rapidly in recent years, however, the genetic pathogenesis is largely unknown on account of rare cases, especially for those patients who are diagnosed with three or more tumors. Under these circumstances, whole-exome sequencing (WES) may help to provide more comprehensive genomic information and guidance to proper therapeutic strategies. Here, we presented a rare case of a 66-year-old Chinese male patient who was diagnosed with synchronous triple primary malignancies: esophageal squamous cell carcinoma (ESCC), lung adenocarcinoma (LA), and hepatocellular carcinoma (HCC). Tumors were surgically removed within 3 months. WES was performed when the patient suffered from cancer recurrence and tumor-specific neoantigens were predicted. Each tumor displayed a distinct somatic mutation profile, providing direct evidence of independent origins. No shared driver gene mutation or neoantigen was detected among the three tumors. Two germline alterations of cancer susceptibility genes—SPINK1 c.194 + 2T>C and JAK3 c.425G>A were identified. This case is the first report of synchronous primary triple cancers covering the esophagus, lung, and liver. Our findings highlight the complexities of MPMs that even when under identical germline genetic backgrounds, the occurrence of MPMs can be a random event and driven by distinct somatic gene mutations. Synchronous multiple primary cancers that originated from different organs may not have common therapeutic gene targets, and it can be difficult to find a treatment to cover all the tumors.

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Whole-Exome Sequencing Identifies Somatic Mutations Associated With Lung Cancer Metastasis to the Brain

10.21203/rs.3.rs-74758/v1 ◽

2020 ◽

Author(s):

Zhenghao Liu ◽

Meiguang Zheng ◽

Bingxi Lei ◽

Zhiwei Zhou ◽

Yutao Huang ◽

...

Keyword(s):

Lung Cancer ◽

Brain Metastasis ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Cancer Metastasis ◽

Gene Mutations ◽

Driver Gene ◽

Cancer Driver ◽

Lung Cancer Metastasis ◽

Whole Exome

Abstract Background: Lung cancer is the most aggressive cancer which representing one-quarter of all cancer-related deaths, and metastatic spread accounts for >70% of these deaths, especially brain metastasis. Metastasis associated mutations are important biomarkers for metastasis prediction and outcome improvement. Methods: In this study, we applied whole-exome sequencing to identify potential metastasis related mutation in 12 paired lung cancer and brain metastasis samples. Results: We identified 1,702 SNVs and 6,131 mutation events in 1,220 genes. Furthermore, we identified several lung cancer metastases associated genes (KMT2C, AHNAK2). A mean of 3.1 driver gene mutation events per tumor with the dN/dS of 2.13 indicating a significant enrichment for cancer driver gene mutations. Mutation spectrum analysis found lung-brain metastasis samples have more similar Ti/Tv(transition/transversion) profile with brain cancer in which C>T transitions are more frequently while lung cancer has more C>A transversion. We also found the most important tumor onset and metastasis pathways such as chronic myeloid leukemia, ErbB signaling pathway and glioma pathway. Finally, we identified a significant survival associated mutation gene ERF in both TCGA (P=0.01) and our dataset (P=0.012). Conclusion: In summary, we conducted a pairwise lung-brain metastasis based exome-wide sequencing and identified some novel metastasis related mutations which provided potential biomarkers for prognosis and targeted therapeutics.

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Abstract 4281: Identification of putative cancer susceptibility genes through whole exome sequencing of a family presenting hereditary colorectal cancer

10.1158/1538-7445.am2017-4281 ◽

2017 ◽

Author(s):

Giovana T. Torrezan ◽

Anna Smirnova ◽

Felipe C. Silva ◽

Erika M. Santos ◽

Renan Valieris ◽

...

Keyword(s):

Colorectal Cancer ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Cancer Susceptibility ◽

Susceptibility Genes ◽

Hereditary Colorectal Cancer ◽

Cancer Susceptibility Genes ◽

Whole Exome

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Whole-exome sequencing identifies somatic mutations and intratumor heterogeneity in inflammatory breast cancer

npj Breast Cancer ◽

10.1038/s41523-021-00278-w ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Rui Luo ◽

Weelic Chong ◽

Qiang Wei ◽

Zhenchao Zhang ◽

Chun Wang ◽

...

Keyword(s):

Breast Cancer ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Inflammatory Breast Cancer ◽

Somatic Mutations ◽

Gene Mutations ◽

Intratumor Heterogeneity ◽

Driver Gene ◽

Tissue Samples ◽

Whole Exome

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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Abstract LB-184: Identification of breast cancer susceptibility genes using whole exome sequencing

10.1158/1538-7445.am10-lb-184 ◽

2010 ◽

Author(s):

Ella Thompson ◽

Jason Ellul ◽

Jason Li ◽

Maria Doyle ◽

Ian Campbell

Keyword(s):

Breast Cancer ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Cancer Susceptibility ◽

Breast Cancer Susceptibility ◽

Susceptibility Genes ◽

Cancer Susceptibility Genes ◽

Whole Exome ◽

Breast Cancer Susceptibility Genes

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Early exploration of two candidate breast cancer susceptibility genes identified by whole-exome sequencing

Hereditary Cancer in Clinical Practice ◽

10.1186/1897-4287-10-s2-a91 ◽

2012 ◽

Vol 10 (Suppl 2) ◽

pp. A91

Author(s):

R Blanc ◽

A Jammot ◽

T Nguyen-Dumont ◽

ZL Teo ◽

FA Odefrey ◽

...

Keyword(s):

Breast Cancer ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Cancer Susceptibility ◽

Breast Cancer Susceptibility ◽

Susceptibility Genes ◽

Cancer Susceptibility Genes ◽

Whole Exome ◽

Breast Cancer Susceptibility Genes ◽

Early Exploration

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Identification of breast cancer susceptibility genes using whole exome sequencing

Hereditary Cancer in Clinical Practice ◽

10.1186/1897-4287-10-s2-a41 ◽

2012 ◽

Vol 10 (Suppl 2) ◽

pp. A41

Author(s):

E Thompson ◽

M Doyle ◽

J Ellul ◽

J Li ◽

I Campbell

Keyword(s):

Breast Cancer ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Cancer Susceptibility ◽

Breast Cancer Susceptibility ◽

Susceptibility Genes ◽

Cancer Susceptibility Genes ◽

Whole Exome ◽

Breast Cancer Susceptibility Genes

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The identification of novel gene mutations for degenerative lumbar spinal stenosis using whole-exome sequencing in a Chinese cohort

BMC Medical Genomics ◽

10.1186/s12920-021-00981-4 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Xin Jiang ◽

Dong Chen

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Spinal Stenosis ◽

Lumbar Spinal Stenosis ◽

Gene Mutations ◽

Specific Gene ◽

Single Nucleotide ◽

Degenerative Lumbar Spinal Stenosis ◽

Whole Exome ◽

Lumbar Spinal

Abstract Background Degenerative lumbar spinal stenosis (DLSS) is a common lumbar disease that requires surgery. Previous studies have indicated that genetic mutations are implicated in DLSS. However, studies on specific gene mutations are scarce. Whole-exome sequencing (WES) is a valuable research tool that identifies disease-causing genes and could become an effective strategy to investigate DLSS pathogenesis. Methods From January 2016 to December 2017, we recruited 50 unrelated patients with symptoms consistent with DLSS and 25 unrelated healthy controls. We conducted WES and exome data analysis to identify susceptible genes. Allele mutations firstly identified potential DLSS variants in controls to the patients’ group. We conducted a site-based association analysis to identify pathogenic variants using PolyPhen2, SIFT, Mutation Taster, Combined Annotation Dependent Depletion, and Phenolyzer algorithms. Potential variants were further confirmed using manual curation and validated using Sanger sequencing. Results In this cohort, the major classification variant was missense_mutation, the major variant type was single nucleotide polymorphism (SNP), and the major single nucleotide variation was C > T. Multiple SNPs in 34 genes were identified when filtered allele mutations in controls to retain only patient mutations. Pathway enrichment analyses revealed that mutated genes were mainly enriched for immune response-related signaling pathways. Using the Novegene database, site-based associations revealed several novel variants, including HLA-DRB1, PARK2, ACTR8, AOAH, BCORL1, MKRN2, NRG4, NUP205 genes, etc., were DLSS related. Conclusions Our study revealed that deleterious mutations in several genes might contribute to DLSS etiology. By screening and confirming susceptibility genes using WES, we provided more information on disease pathogenesis. Further WES studies incorporating larger DLSS patient cohorts are required to comprehend the genetic landscape of DLSS pathophysiology fully.

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Whole-exome sequencing associates novel CSMD1 gene mutations with familial Parkinson disease

Neurology Genetics ◽

10.1212/nxg.0000000000000177 ◽

2017 ◽

Vol 3 (5) ◽

pp. e177 ◽

Cited By ~ 12

Author(s):

Javier Ruiz-Martínez ◽

Luis J. Azcona ◽

Alberto Bergareche ◽

Jose F. Martí-Massó ◽

Coro Paisán-Ruiz

Keyword(s):

Parkinson Disease ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Genome Wide Association Study ◽

Single Gene ◽

Gene Mutations ◽

Complement Control Protein ◽

Genome Wide ◽

Whole Exome ◽

A Genome

Objective:Despite the enormous advancements made in deciphering the genetic architecture of Parkinson disease (PD), the majority of PD is idiopathic, with single gene mutations explaining only a small proportion of the cases.Methods:In this study, we clinically evaluated 2 unrelated Spanish families diagnosed with PD, in which known PD genes were previously excluded, and performed whole-exome sequencing analyses in affected individuals for disease gene identification.Results:Patients were diagnosed with typical PD without relevant distinctive symptoms. Two different novel mutations were identified in the CSMD1 gene. The CSMD1 gene, which encodes a complement control protein that is known to participate in the complement activation and inflammation in the developing CNS, was previously shown to be associated with the risk of PD in a genome-wide association study.Conclusions:We conclude that the CSMD1 mutations identified in this study might be responsible for the PD phenotype observed in our examined patients. This, along with previous reported studies, may suggest the complement pathway as an important therapeutic target for PD and other neurodegenerative diseases.

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