Assessment of the clinical relevance of 17q25.3 copy number and three-dimensional telomere organization in non-small lung cancer patients

Sunpaweravong, Patrapim; Thu, Kelsie L.; Lam, Wan L.; Mai, Sabine

doi:10.1007/s00432-015-2080-5

Cited by 8 publications

(6 citation statements)

References 17 publications

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“…Further, Sunpaweravong et al . 39 have implicated that gains of cytoband 17q25.3 are found in 61% lung cancer patients, underscoring a potential biological role for the genes within this region in the progression of lung cancer, which further substantiates the fact that there are many oncogenes located at chromosome 17. Significantly, loss of heterozygosity for the short arm of chromosome 17 has been demonstrated in a 4-year-old boy with GBM 40 .…”

Section: Discussionmentioning

confidence: 82%

A RNA sequencing-based six-gene signature for survival prediction in patients with glioblastoma

Zuo

Zhang

Wang

2019

Sci Rep

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Glioblastoma (GBM) is an aggressive tumor of the central nervous system that has poor prognosis despite extensive therapy. Therefore, it is essential to identify a gene expression-based signature for predicting GBM prognosis. The RNA sequencing data of GBM patients from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases were employed in our study. The univariate and multivariate regression models were utilized to assess the relative contribution of each gene to survival prediction in both cohorts, and the common genes in two cohorts were identified as a final prognostic model. A prognostic risk score was calculated based on the prognostic gene signature. This prognostic signature stratified the patients into the low- and high-risk groups. Multivariate regression and stratification analyses were implemented to determine whether the gene signature was an independent prognostic factor. We identified a 6-gene signature through univariate and multivariate regression models. This prognostic signature stratified the patients into the low- and high-risk groups, implying improved and poor outcomes respectively. Multivariate regression and stratification analyses demonstrated that the predictive value of the 6-gene signature was independent of other clinical factors. This study highlights the significant implications of having a gene signature as a prognostic predictor in GBM, and its potential application in personalized therapy.

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Section: Discussionmentioning

confidence: 82%

A RNA sequencing-based six-gene signature for survival prediction in patients with glioblastoma

Zuo

Zhang

Wang

2019

Sci Rep

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“…Sunpaweravong et al reported that gains of chromosome 17 were observed in approximately one third (38.9%) of NSCLC patients while a majority (61%) harbored clonal gains of cytoband 17q25.3. These patients also had a tendency towards poorer survival outcome ( 2 ).…”

Section: Discussionmentioning

confidence: 99%

“…c-Myc, as a transcription and replication factor, regulates multiple genes that control cell growth in varied cancer types including NSCLC. Copy number gains of cytoband 17q25.3, along with chromosome 17, have been reported in patients having NSCLC, emphasizing its clinical significance as a potential molecular target for therapy in this cancer ( 2 ). In pre-clinical studies, the upregulation of c-Myc has been found to lead to accelerated tumor development associated with duplication of the syntenic human cytoband 17q25.3, emphasizing the important role of this region in tumorigenesis ( 3 , 4 ).…”

Section: Introductionmentioning

confidence: 99%

Copy number gains of chromosome 17 identified by dual in situ hybridization in non-small cell lung cancer tissue correlate with overexpression of c-Myc

Sunpaweravong

Thongwatchara

Sangthong

et al. 2022

Transl Cancer Res TCR

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Background c-Myc regulates multiple genes involved in cell proliferation in various cancer types including non-small cell lung cancer (NSCLC). Copy number gains of cytoband 17q25.3, along with chromosome 17, have been reported in NSCLC patients, emphasizing the clinical significance as a potential molecular target for therapy. The upregulation of c-Myc has been found to accelerate tumor development associated with duplication of the syntenic human cytoband 17q25.3. This study aimed to explore and compare the correlations of chromosome 17 copy number and c-Myc expression in NSCLC with the paired-normal respiratory epithelium and to examine their role as potential molecular targets for NSCLC therapy. Methods A total of 66 NSCLC tissue samples with paired-normal respiratory epithelium were examined. The copy number of chromosome 17 was determined by human epidermal growth factor receptor 2 ( HER2 )/centromeric enumeration probe of chromosome 17 (CEP17) dual in situ hybridization (DISH). Results Copy number gains of chromosome 17 were identified in 8 of 60 (13.3%) available NSCLC specimens. No copy number gains of chromosome 17 were demonstrated in the paired-normal respiratory epithelium. The mean HER2 (1.2±0.3) and CEP17 (1.4±0.3) copy numbers of the normal respiratory epithelium were significantly lower than those of the NSCLC tissue [1.8±1.0 vs. 2.0±0.8, respectively (P<0.001)]. Twelve of 66 (18.2%) NSCLC patients had overexpression of c-Myc. Five (41.7%) of the patients whose tumors positive for c-Myc had HER2 gene amplification [1] or copy number gain of chromosome 17 [4]. HER2 gene amplification or copy number gain of chromosome 17 and high expression of c-Myc were associated with decreased overall survival. Conclusions Both biomarkers deserve further investigation to identify NSCLC patients with poorer survival outcomes requiring better therapeutic approaches.

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“…A common genetic feature of neuroblastoma and medulloblastoma is segmental gain of chromosome 17q, which in both diseases is a predictor of poor prognosis [ 8 , 45 , 52 ]. Frequent gain of chromosome 17q is also observed in cancers with epithelial, neural or hematopoietic origin [ 53 , 54 , 55 , 56 , 57 , 58 ]. This suggests that one or multiple genes important for tumorigenesis are located on 17q.…”

Section: Discussionmentioning

confidence: 99%

PPM1D Is a Therapeutic Target in Childhood Neural Tumors

Milosevic

Treis

Fransson

et al. 2021

Cancers

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Childhood medulloblastoma and high-risk neuroblastoma frequently present with segmental gain of chromosome 17q corresponding to aggressive tumors and poor patient prognosis. Located within the 17q-gained chromosomal segments is PPM1D at chromosome 17q23.2. PPM1D encodes a serine/threonine phosphatase, WIP1, that is a negative regulator of p53 activity as well as key proteins involved in cell cycle control, DNA repair and apoptosis. Here, we show that the level of PPM1D expression correlates with chromosome 17q gain in medulloblastoma and neuroblastoma cells, and both medulloblastoma and neuroblastoma cells are highly dependent on PPM1D expression for survival. Comparison of different inhibitors of WIP1 showed that SL-176 was the most potent compound inhibiting medulloblastoma and neuroblastoma growth and had similar or more potent effects on cell survival than the MDM2 inhibitor Nutlin-3 or the p53 activator RITA. SL-176 monotherapy significantly suppressed the growth of established medulloblastoma and neuroblastoma xenografts in nude mice. These results suggest that the development of clinically applicable compounds inhibiting the activity of WIP1 is of importance since PPM1D activating mutations, genetic gain or amplifications and/or overexpression of WIP1 are frequently detected in several different cancers.

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Assessment of the clinical relevance of 17q25.3 copy number and three-dimensional telomere organization in non-small lung cancer patients

Cited by 8 publications

References 17 publications

A RNA sequencing-based six-gene signature for survival prediction in patients with glioblastoma

A RNA sequencing-based six-gene signature for survival prediction in patients with glioblastoma

Copy number gains of chromosome 17 identified by dual in situ hybridization in non-small cell lung cancer tissue correlate with overexpression of c-Myc

PPM1D Is a Therapeutic Target in Childhood Neural Tumors

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