Genetic variations using whole-exome sequencing might predict response for neoadjuvant chemoradiotherapy in locally advanced rectal cancer

Lee, In Hee; Kang, Keunsoo; Kang, Byung Woog; Lee, Soo Jung; Bae, Woo Kyun; Hwang, Jun Eul; Kim, Hye Jin; Park, Suyeon; Park, Jun Seok; Choi, Gyu Seog; Kim, Jong Gwang

doi:10.1007/s12032-018-1202-8

Cited by 16 publications

(14 citation statements)

References 31 publications

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“…Considerable efforts have been devoted to identifying genetic biomarkers associated with NCRT response in LARC patients. 21 , 22 Unlike conventional bioinformatics methods, WGCNA can facilitate network-based gene screening methods, classify genes with highly similar coexpression patterns into separate modules, and identify those modules highly associated with clinical traits. 9 , 10 Currently, WGCNA has been used to identify network-centric genes in rectal cancer research; 14 , 23 however, WGCNA has not been extensively utilized to explore genes associated with NCRT response.…”

Section: Discussionmentioning

confidence: 99%

<p>A Four Gene-Based Risk Score System Associated with Chemoradiotherapy Response and Tumor Recurrence in Rectal Cancer by Co-Expression Network Analysis</p>

Sun¹,

Zhang²,

Wu³

et al. 2020

OTT

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Resistance to neoadjuvant chemoradiotherapy (NCRT) and tumor recurrence presents a major clinical problem in locally advanced rectal cancer (LARC) patients. This study aimed to explore a genetic risk score related to NCRT response and tumor recurrence in rectal cancer after NCRT. Materials and Methods: Weighted gene co-expression network analysis was employed to identify hub genes associated with NCRT response from the GSE93375 dataset. Prognostic hub genes were determined using Cox regression analysis and associated with disease-free survival (DFS). A risk score system was constructed and the prognostic significance of the risk score was validated in our patient cohort. A predictive nomogram for DFS was developed and validated internally. Results: The Tan module had the highest correlations with NCRT response. Ten hub genes (COL15A1, THBS2, ITGB1, MMP2, CD34, SPARC, NOTCH3, PDGFRB, DCN, and SERPINH1) were associated with NCRT response. Immunostaining expression of four genes (NOTCH3, SPARC, DCN, and ITGB1) was found to be significantly associated with both NCRT response and DFS in our patient cohort and was selected to build a prognostic risk score for DFS as follows: risk score= (0.6188×Exp NOTCH3) + (0.6511×Exp SPARC) + (−0.2976×Exp DCN) + (1.0035×Exp ITGB1). Using this risk score, patients could be separated into high-and low-risk groups for tumor recurrence. A nomogram that incorporated the risk score, ypTNM stage, and tumor regression grade (TRG) was constructed and utilized to predict DFS in LARC patients. Conclusion: The four-gene expression-based risk score system presented here could be potentially used for predicting tumor recurrence in LARC patients after NCRT.

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Section: Discussionmentioning

confidence: 99%

<p>A Four Gene-Based Risk Score System Associated with Chemoradiotherapy Response and Tumor Recurrence in Rectal Cancer by Co-Expression Network Analysis</p>

Sun¹,

Zhang²,

Wu³

et al. 2020

OTT

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“…DNAH14 genetic rare variation introduces a missense amino acid substitution in p.Leu4096Pro, in exon 77. Genetic variation in DNAH14 rs3105571 has been described and is significantly associated with pathologic complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer [13]. Another clinically relevant frameshift deletion was found in MLLT1 gene, p.Gln461fs, in exon 6.…”

Section: Selection Of Center-specific or Periphery-specific Variantsmentioning

confidence: 99%

Exome sequencing of glioblastoma-derived cancer stem cells reveals rare clinically relevant frameshift deletion in MLLT1 gene

et al. 2022

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Background Glioblastoma multiforme (GBM) is a heterogeneous CNS neoplasm which causes significant morbidity and mortality. One reason for the poor prognostic outcome of GBM is attributed to the presence of cancer stem cells (CSC) which confer resistance against standard chemo- and radiotherapeutics modalities. Two types of GBM-associated CSC were isolated from the same patient: tumor core- (c-CSC) and peritumor tissue-derived cancer stem cells (p-CSC). Our experiments are focused on glioblastoma–IDH-wild type, and no disease-defining alterations were present in histone, BRAF or other genes. Methods In the present study, potential differences in genetic variants between c-CSC versus p-CSC derived from four GBM patients were investigated with the aims of (1) comparing the exome sequences between all the c-CSC or p-CSC to identify the common variants; (2) identifying the variants affecting the function of genes known to be involved in cancer origin and development. Results By comparative analyses, we identified common gene single nucleotide variants (SNV) in all GBM c-CSC and p-CSC, a potentially deleterious variant was a frameshift deletion at Gln461fs in the MLLT1 gene, that was encountered only in p-CSC samples with different allelic frequency. Conclusions We discovered a potentially harmful frameshift deletion at Gln461fs in the MLLT1 gene. Further investigation is required to confirm the presence of the identified mutations in patient tissue samples, as well as the significance of the frameshift mutation in the MLLT1 gene on GBM biology and response to therapy based on genomic functional experiments.

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“…DNAH14 genetic rare variation introduces a missense amino acid substitution in p.Leu4096Pro, in exon 77. Genetic variation in DNAH14 rs3105571 has been described and is signi cantly associated with pathologic complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer (13). Another clinically relevant frameshift deletion was found in MLLT1 gene, p.Gln461fs, in exon 6.…”

Section: Selection Of Center-speci C or Periphery-speci C Variantsmentioning

confidence: 99%

Exome Sequencing of Glioblastoma-Derived Cancer Stem Cells Reveals Rare Clinically Relevant Frameshift Deletion in MLLT1 Gene

Marei

Althani

Afifi

et al. 2021

Preprint

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Background: Glioblastoma multiforme (GBM) is a heterogeneous CNS neoplasm which causes significant morbidity and mortality. One reason for the poor prognostic outcome of GBM is attributed to the presence of cancer stem cells (CSC) which confer resistance against standard chemo- and radiotherapeutics modalities. Two types of GBM-associated CSC were isolated from the same patient: tumor core- (c-CSC) and peritumor tissue-derived cancer stem cells (p-CSC).Methods: In the present study, potential differences in genetic variants between c-CSC versus p-CSC derived from four GBM patients were investigated with the aims of 1) comparing the exome sequences between all the c-CSC or p-CSC to identify the common variants; 2) identifying the variants affecting the function of genes known to be involved in cancer origin and development.Results: By comparative analyses, we identified common gene single nucleotide variants (SNV) in all GBM c-CSC and p-CSC, a potentially deleterious variant was a frameshift deletion at Gln461fs in the MLLT1 gene, that was encountered only in p-CSC samples with different allelic frequency.Conclusions: Our study supports the hypothesis that the varied genetic composition of GBM-associated c-CSC and p-CSC may be involved in different therapeutic responses or the recurrent nature of GBM.

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Genetic variations using whole-exome sequencing might predict response for neoadjuvant chemoradiotherapy in locally advanced rectal cancer

Cited by 16 publications

References 31 publications

<p>A Four Gene-Based Risk Score System Associated with Chemoradiotherapy Response and Tumor Recurrence in Rectal Cancer by Co-Expression Network Analysis</p>

<p>A Four Gene-Based Risk Score System Associated with Chemoradiotherapy Response and Tumor Recurrence in Rectal Cancer by Co-Expression Network Analysis</p>

Exome sequencing of glioblastoma-derived cancer stem cells reveals rare clinically relevant frameshift deletion in MLLT1 gene

Exome Sequencing of Glioblastoma-Derived Cancer Stem Cells Reveals Rare Clinically Relevant Frameshift Deletion in MLLT1 Gene

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