Comprehensive genomic profiling of different subtypes of nasopharyngeal carcinoma reveals similarities and differences to guide targeted therapy

Ali, Siraj M.; Yao, Ming; Yao, Jie; Wang, Jing; Cheng, Yu‐Wei; Schrock, Alexa B.; Chirn, Gung-Wei; Chen, Hui; Mu, Shuo; Gay, Laurie M.; Elvin, Julia A.; Suh, James; Miller, Vincent A.; Stephens, Philip J.; Ross, Jeffrey S.; Wang, Kai

doi:10.1002/cncr.30781

Cited by 43 publications

(41 citation statements)

References 49 publications

(91 reference statements)

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“…1 These are thoughtful queries that must be addressed around the classification of tumors. 1 These are thoughtful queries that must be addressed around the classification of tumors.…”

Section: Funding Supportmentioning

confidence: 99%

“…In fact, from the tumor sites shown by the authors in Table 1, 1 it is highly possible that tumors from other head and neck regions, instead of the nasopharynx, were included in their genome profiling. 1 In our opinion, the lack of accurate histological classification and evidence diminishes the clinical value of their findings regarding both major and rare NPC subtypes. 1 In fact, to the best of our knowledge, all 4 NPC wholeexome sequencing studies published from 2014 through 2017 3-6 consistently demonstrated that an IDH2 (or even isocitrate dehydrogenase 1, IDH1) mutation event is absolutely rare in NPC.…”

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confidence: 94%

“…For example, Table 1 in the study by Ali et al indicated that only 6 of 108 NPUC tumors originally were obtained from the "nasopharynx and paranasal sinuses." 1 In fact, to the best of our knowledge, all 4 NPC wholeexome sequencing studies published from 2014 through 2017 3-6 consistently demonstrated that an IDH2 (or even isocitrate dehydrogenase 1, IDH1) mutation event is absolutely rare in NPC. Furthermore, the remaining majority of NPUC tumors (102 cases) appeared to be largely obtained from the nasal cavity rather than the nasopharynx.…”

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confidence: 96%

“…1 However, with regard to their study, we believe several issues are of concern. 1 However, with regard to their study, we believe several issues are of concern.…”

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confidence: 99%

“…Because EBV latent infection is a well-known characteristic of nonkeratinizing NPC in endemic regions, we believe that the EBV status, as determined by EBER in situ hybridization, should be performed carefully for all cases presented in the study by Ali et al 1 This is particularly important because to our knowledge none of the NPC genome studies published to date have had enough power in terms of case number to compare the genomic profiles of EBV-positive and EBV-negative NPC cases. This assay is performed routinely for the diagnosis of NPC by pathology laboratories in endemic regions (eg, Singapore and Hong Kong).…”

mentioning

confidence: 99%

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Genomic profiles of nasopharyngeal carcinoma: The importance of histological subtyping and Epstein‐Barr virus in situ assays

Lui

2017

Cancer

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“…1 These are thoughtful queries that must be addressed around the classification of tumors. 1 These are thoughtful queries that must be addressed around the classification of tumors.…”

Section: Funding Supportmentioning

confidence: 99%

mentioning

confidence: 94%

mentioning

confidence: 96%

“…1 However, with regard to their study, we believe several issues are of concern. 1 However, with regard to their study, we believe several issues are of concern.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

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Genomic profiles of nasopharyngeal carcinoma: The importance of histological subtyping and Epstein‐Barr virus in situ assays

Lui

2017

Cancer

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Links between melanoma germline risk loci, driver genes and comorbidities: insight from a tissue‐specific multi‐omic analysis

Pudjihartono,

Golovina,

Fadason

et al. 2024

Molecular Oncology

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Genome‐wide association studies (GWAS) have associated 76 loci with the risk of developing melanoma. However, understanding the molecular basis of such associations has remained a challenge because most of these loci are in non‐coding regions of the genome. Here, we integrated data on epigenomic markers, three‐dimensional (3D) genome organization, and expression quantitative trait loci (eQTL) from melanoma‐relevant tissues and cell types to gain novel insights into the mechanisms underlying melanoma risk. This integrative approach revealed a total of 151 target genes, both near and far away from the risk loci in linear sequence, with known and novel roles in the etiology of melanoma. Using protein–protein interaction networks, we identified proteins that interact—directly or indirectly—with the products of the target genes. The interacting proteins were enriched for known melanoma driver genes. Further integration of these target genes into tissue‐specific gene regulatory networks revealed patterns of gene regulation that connect melanoma to its comorbidities. Our study provides novel insights into the biological implications of genetic variants associated with melanoma risk.

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Pembrolizumab in men with heavily treated metastatic castrate‐resistant prostate cancer

et al. 2019

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Background Pembrolizumab is approved for patients with metastatic, microsatellite instability (MSI)‐high or mismatch repair‐deficient (dMMR) solid tumors. However, very few men with prostate cancer were included in these initial studies. Methods We performed a single institution retrospective review of men with metastatic castrate‐resistant prostate cancer (mCRPC) who were treated with pembrolizumab. The primary objective was to describe the clinical efficacy of pembrolizumab associated with patient and genomic characteristics. Results We identified 48 men who received ≥1 cycle of pembrolizumab for mCRPC. Of these, 94% (45/48) had ≥3 prior lines of therapy for mCRPC. Somatic tumor sequencing was available in 18/48 men (38%). We found that 17% (8/48) had a ≥50% confirmed PSA decline with pembrolizumab, and 8% (4/48) had a ≥90% PSA decline with durations of response ranging from 3.1 to 16.3 months. Two of these four men had mutations in LRP1b , one of whom also had MSH2 loss and was MSI‐H and TMB‐high. Despite prior progression on enzalutamide, 48% (23/48) of men were treated with concurrent enzalutamide. The median PSA progression‐free‐survival was 1.8 months (range 0.4‐13.7 months), with 31% of patients remaining on pembrolizumab therapy and 54% of men remain alive with a median follow‐up of 7.1 months. Conclusions In a heavily pretreated population of men with mCRPC, pembrolizumab was associated with a ≥50% PSA decline in 17% (8/48) of men, including a dramatic ≥90% PSA response in 8% (4/48), two of whom harbored pathogenic LRP1b mutations suggesting that LRP1b mutations may enrich for PD‐1 inhibitor responsiveness in prostate cancer.

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Comprehensive genomic profiling of different subtypes of nasopharyngeal carcinoma reveals similarities and differences to guide targeted therapy

Cited by 43 publications

References 49 publications

Genomic profiles of nasopharyngeal carcinoma: The importance of histological subtyping and Epstein‐Barr virus in situ assays

Genomic profiles of nasopharyngeal carcinoma: The importance of histological subtyping and Epstein‐Barr virus in situ assays

Links between melanoma germline risk loci, driver genes and comorbidities: insight from a tissue‐specific multi‐omic analysis

Pembrolizumab in men with heavily treated metastatic castrate‐resistant prostate cancer

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