Small-Cell Carcinomas of the Bladder and Lung Are Characterized by a Convergent but Distinct Pathogenesis

Chang, Matthew T.; Penson, A.; Desai, Neil B.; Socci, Nicholas D.; Shen, Ronglai; Seshan, Venkatraman; Kundra, Ritika; Abeshouse, Adam; Viale, Agnès; Eugene, K.; Hao, Xueli; Reuter, Victor E.; Rudin, Charles M.; Bochner, Bernard H.; Rosenberg, Jacob; Bajorin, Dean F.; Schultz, Nikolaus; Berger, Michael F.; Iyer, Gopa; Solit, David B.; Al‐Ahmadie, Hikmat; Taylor, Barry S.

doi:10.1158/1078-0432.ccr-17-2655

Cited by 94 publications

(103 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Deletion of CDKN2A and amplification of CCND1 are commonly found in conventional urothelial carcinoma, whereas the inverse has been reported for phenotypic NE cancers (33)(34)(35). The NE-like cases in our study had profiles consistent with these latter reports, including higher expression of CDKN2A and lower expression of CCDN1 relative to basal or luminal cases ( Supplementary Fig.…”

Section: Ne-like Tumors Are Defined By Unique Biological Characteristicssupporting

confidence: 87%

“…The different histologic subtypes of bladder cancer frequently occur together with conventional urothelial carcinoma, and the usual dictum is that these subtypes share a common origin with the concurrent urothelial carcinoma (33,34). It is, therefore, conceivable that the NE-like tumors with conventional urothelial morphology but a NE transcriptional program represent an intermediate stage in the evolution towards a histologic NE phenotype.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Molecular Characterization of Neuroendocrine-like Bladder Cancer

Costa

Gibb²,

Bivalacqua³

et al. 2019

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Neuroendocrine (NE) bladder carcinoma is a rare and aggressive variant. Molecular subtyping studies have found that 5% to 15% of muscle-invasive bladder cancer (MIBC) have transcriptomic patterns consistent with NE bladder cancer in the absence of NE histology. The clinical implications of this NE-like subtype have not been explored in depth.Experimental Design: Transcriptome-wide expression profiles were generated for MIBC collected from 7 institutions and clinical-use of Decipher Bladder. Using unsupervised clustering, we generated a clustering solution on a prospective training cohort (PTC; n ¼ 175), developed single-sample classifiers to predict NE tumors, and evaluated the resultant models on a testing radical cystectomy (RC) cohort (n ¼ 225). A random forest model was finalized and applied to 5 validation cohorts (n ¼ 1302). Uni-and multivariable survival analyses were used to characterize clinical outcomes. Results:In the training cohort (PTC), hierarchical clustering using an 84-gene panel showed a cluster of 8 patients (4.6%) with highly heterogeneous expression of NE markers in the absence of basal or luminal marker expression. NE-like tumors were identified in 1% to 6.6% of cases in validation cohorts. Patients with NE-like tumors had significantly worse 1-year progression-free survival (65% NE-like vs. 82% overall; P ¼ 0.046) and, after adjusting for clinical and pathologic factors, had a 6.4-fold increased risk of all-cause mortality (P ¼ 0.001). IHC confirmed the neuronal character of these tumors.Conclusions: A single-patient classifier was developed that identifies patients with histologic urothelial cancer harboring a NE transcriptomic profile. These tumors represent a high-risk subgroup of MIBC, which may require different treatment. a P <0.05.Batista da Costa et al.

show abstract

Section: Ne-like Tumors Are Defined By Unique Biological Characteristicssupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Molecular Characterization of Neuroendocrine-like Bladder Cancer

Costa

Gibb²,

Bivalacqua³

et al. 2019

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…Samples harbored 1p19q codeletion if the inferred copy number at the 1p and 19q regions was less than or equal to half of the copy number at 1q and 19p regions. The clonality of BRAF mutations was estimated from MSK-IMPACT samples as described previously (15). Briefly, allele-specific copy number was used to estimate local BRAF-spanning copy number and tumor purity, with which the most likely fraction of cancer cells harboring the mutation was derived.…”

Section: Translational Relevancementioning

confidence: 99%

Genomic Correlates of Disease Progression and Treatment Response in Prospectively Characterized Gliomas

Jonsson

Lin

Young

et al. 2019

Clinical Cancer Research

Self Cite

113

View full text Add to dashboard Cite

Purpose: The genomic landscape of gliomas has been characterized and now contributes to disease classification, yet the relationship between molecular profile and disease progression and treatment response remain poorly understood. Experimental Design: We integrated prospective clinical sequencing of 1,004 primary and recurrent tumors from 923 glioma patients with clinical and treatment phenotypes. Results: Thirteen percent of glioma patients harbored a pathogenic germline variant, including a subset associated with heritable genetic syndromes and variants mediating DNA repair dysfunctions (29% of the total) that were associated with somatic biallelic inactivation and mechanism-specific somatic phenotypes. In astrocytomas, genomic alterations in effectors of cell-cycle progression correlated with aggressive disease independent of IDH mutation status, arose preferentially in enhancing tumors (44% vs. 8%, P < 0.001), were associated with rapid disease progression following tumor recurrence (HR ¼ 2.6, P ¼ 0.02), and likely preceded the acquisition of alkylating therapyassociated somatic hypermutation. Thirty-two percent of patients harbored a potentially therapeutically actionable lesion, of whom 11% received targeted therapies. In BRAFmutant gliomas, response to agents targeting the RAF/MEK/ ERK signaling axis was influenced by the type of mutation, its clonality, and its cellular and genomic context. Conclusions: These data reveal genomic correlates of disease progression and treatment response in diverse types of glioma and highlight the potential utility of incorporating genomic information into the clinical decision-making for patients with glioma.

show abstract

“…As bladder small cell carcinoma is histologically similar to small cell carcinoma of the lung, it is not surprising that these 2 tumors have overlapping molecular profiles and develop through a similar sequence of genomic alterations. 70…”

Section: Bladder Urothelial Carcinoma Variantsmentioning

confidence: 99%

Bladder Cancer in the Genomic Era

Guo

Czerniak

2019

Archives of Pathology &Amp; Laboratory Medicine

View full text Add to dashboard Cite

Context.-Bladder cancer is a heterogeneous disease that exhibits a wide spectrum of clinical and pathologic features. The classification of bladder cancer has been traditionally based on morphologic assessment with the aid of immunohistochemistry. However, recent genomic studies have revealed that distinct alterations of DNA and RNA in bladder cancer may underlie its diverse clinicopathologic features, leading to a novel molecular classification of this common human cancer.Objective.-To update recent developments in genomic characterization of bladder cancer, which may shed insights on the molecular mechanisms underlying the origin of bladder cancer, dual-track oncogenic pathways, intrinsic molecular subtyping, and development of histologic variants. Data Sources.-Peer-reviewed literature retrieved from PubMed search and authors' own research.Conclusions.-Bladder cancer is likely to arise from different uroprogenitor cells through papillary/luminal and nonpapillary/basal tracks. The intrinsic molecular subtypes of bladder cancer referred to as luminal and basal exhibit distinct expression signatures, clinicopathologic features, and sensitivities to standard chemotherapy. Genomic characterization of bladder cancer provides new insights to understanding the biological nature of this complex disease, which may lead to more effective treatment.

show abstract

Small-Cell Carcinomas of the Bladder and Lung Are Characterized by a Convergent but Distinct Pathogenesis

Cited by 94 publications

References 35 publications

Molecular Characterization of Neuroendocrine-like Bladder Cancer

Molecular Characterization of Neuroendocrine-like Bladder Cancer

Genomic Correlates of Disease Progression and Treatment Response in Prospectively Characterized Gliomas

Bladder Cancer in the Genomic Era

Contact Info

Product

Resources

About