Amplification of 8p11.23 in cancers and the role of amplicon genes

Voutsadakis, Ioannis A.

doi:10.1016/j.lfs.2020.118729

Cited by 16 publications

(15 citation statements)

References 103 publications

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“…In the present study, we analyzed 33 different cancer types and found that NSD3 expression was highly heterogeneous across the different cancers. In line with previous studies, NSD3 expression was upregulated in LUSC, ESCA, LIHC, and HNSC (33)(34)(35). Some studies have also reported that NSD3 expression is increased in BLCA and COAD [45,46], which is inconsistent with our current results.…”

Section: Discussioncontrasting

confidence: 80%

Prognostic and Immunological Characterization of NSD3 Evaluated Through an Integrative Pan-Cancer Analysis

Liu

Yao

et al. 2021

Preprint

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Background: Nuclear receptor binding SET domain protein-3 (NSD3) has been reported to be a crucial regulator of carcinogenesis as a histone lysine methyltransferase in multiple cancer types. However, the underlying mechanisms have not been clearly delineated. Therefore, we aimed to investigate the expression pattern, prognostic value, and potential function of NSD3 in 33 types of human cancer. Methods: The potential roles of NSD3 were explored using datasets from The Cancer Genome Atlas (TCGA) pan-cancer dataset and an array of bioinformatics methods, including analyses of the relationship between NSD3 expression and prognosis, tumor mutational burden (TMB), microsatellite instability (MSI), DNA amplification, and immune cell inﬁltration across 33 cancer types. Results: Many types of cancers are characterized according to the dysregulation of NSD3, which is associated with the pathological stage of cancer. Patients in our study with higher NDS3 levels, which were attributed to NSD3 copy number amplification, always experienced shorter survival periods. Additionally, NSD3 expression was associated with TMB and MSI in 10 different cancer types. The top five cancers whose NSD3 expression correlated with immune scores were further analyzed. The levels of immune-cell infiltration differed significantly between high and low NSD3-expressing samples in each of the five cancer types. Functional enrichment of the NSD3 co-expressed genes indicated a role for NSD3 in the regulation of immune responses and tumorigenesis. Conclusions: Our study revealed that NSD3 can function as a prognostic marker in various cancers due to its role in tumorigenesis and tumor immunity.

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Section: Discussioncontrasting

confidence: 80%

Prognostic and Immunological Characterization of NSD3 Evaluated Through an Integrative Pan-Cancer Analysis

Liu

Yao

et al. 2021

Preprint

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“…Each tumor contains a median of 19 recurrently aberrant copy-number segments, with a median number of 15 genes in amplified segments and a median of one gene in homozygous deleted segments [24]. As a result, pinpointing to the gene or the genes that are putative driver alterations in each recurrent amplification is a conundrum and represents a more difficult task to identify with certainty compared with recurrent deletions [27]. Several recurrent amplifications in cancer are not primary-site specific, but they are observed in a spectrum of primary cancer types.…”

Section: Discussionmentioning

confidence: 99%

3q26 Amplifications in Cervical Squamous Carcinomas

Voutsadakis

2021

Current Oncology

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Background: Squamous carcinomas of the uterine cervix often carry mutations of the gene encoding for the catalytic sub-unit of kinase PI3K, PIK3CA. The locus of this gene at chromosome 3q26 and neighboring loci are also commonly amplified. The landscape of 3q26-amplified cases have not been previously characterized in detail in cervical cancer. Methods: Published genomic data and associated clinical data from TCGA cervical cancer cohort were analyzed at cBioportal for amplifications in genes at 3q26. The clinical and molecular characteristics of the group of patients with 3q26 amplifications was compared with the group without 3q26 amplifications. Comparative prevalence of amplification and expression of genes at 3q26 in amplified squamous cervical cancer cases were surveyed as well as 3q26 amplifications in cervical cancer cell line databases. Results: Amplification of 3q26 locus is a prevalent molecular lesion in cervical squamous cell carcinomas encountered in about 15% of cases in TCGA cohort of 247 patients. Cancer-related genes commonly amplified from 3q26 include PIK3CA, TBL1XR1, DCUN1D1, SOX2, MECOM, PRKCI, and TERC. Amplified cases do not completely overlap with PIK3CA mutant cases. Differences exist between 3q26-amplified and non-amplified carcinomas in the frequency of mutations and frequency of other amplifications. Most commonly over-expressed genes in 3q26 amplified cases include PIK3CA, TBL1XR1, DCUN1D1, and less commonly SOX2 and PRKCI. Conclusion: The subset of squamous cervical carcinomas with 3q26 amplifications is not overlapping with cancers carrying PIK3CA mutations and contains, besides PIK3CA, other cancer-associated genes that are over-expressed at the mRNA level, including TBL1XR1 and DCUN1D1. DCUN1D1, a regulator of SCF ubiquitin ligase activity, may be a relevant pathogenic player given the importance of ubiquitination and the proteasome in the disease. These observations could form the basis for therapeutic exploitation in this subset of squamous cervical carcinomas.

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“…Its absence could sensitize cells to antimetabolite drugs. Deletions of 1p42 harboring TRIM genes encoding for p53 regulators and amplifications of the 8p11.23 locus harboring several oncogene candidates observed in subsets of breast cancers, squamous lung, esophageal, and bladder carcinomas are also present in pancreatic cancers with neither KRAS mutations nor TP53 mutations [61]. The absence of KRAS and TP53 mutations, together with maintenance of SMAD4 expression, is enriched in a small series of long-term survivors of pancreatic cancer [62].…”

Section: Pancreatic Cancers Without Kras or Tp53 Mutationsmentioning

confidence: 99%

Mutations of p53 associated with pancreatic cancer and therapeutic implications

Voutsadakis

2021

Ann Hepatobiliary Pancreat Surg

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Pancreatic adenocarcinoma is a malignancy with rising incidence and grim prognosis. Despite improvements in therapeutics for treating metastatic pancreatic cancer, this disease is invariably fatal with survival time less than a few years. New molecular understanding of the pathogenesis of pancreatic adenocarcinoma based on efforts led by The Cancer Genome Atlas and other groups has elucidated the landscape of this disease and started to produce therapeutic results, leading to the first introduction of targeted therapies for subsets of pancreatic cancers bearing specific molecular lesions such as BRCA mutations. These efforts have highlighted that subsets of pancreatic cancers are particularly sensitive to chemotherapy. The most common molecular lesions in pancreatic adenocarcinomas are mutations in an oncogene KRAS and the TP53 gene that encodes for tumor suppressor protein p53. This paper will review the landscape of pancreatic cancers, focusing on mutations of p53, a major tumor suppressor protein, in pancreatic cancers and possible therapeutic repercussions.

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Amplification of 8p11.23 in cancers and the role of amplicon genes

Cited by 16 publications

References 103 publications

Prognostic and Immunological Characterization of NSD3 Evaluated Through an Integrative Pan-Cancer Analysis

Prognostic and Immunological Characterization of NSD3 Evaluated Through an Integrative Pan-Cancer Analysis

3q26 Amplifications in Cervical Squamous Carcinomas

Mutations of p53 associated with pancreatic cancer and therapeutic implications

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