ALK amplification and protein expression predict inferior prognosis in neuroblastomas

Wang, Miao; Zhou, Chunju; Sun, Qinnuan; Cai, Rongqin; Yong, Li; Wang, Daye; Gong, Li‐ping

doi:10.1016/j.yexmp.2013.06.002

Cited by 40 publications

(44 citation statements)

References 22 publications

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“…In our earlier analysis, we observed ALK expression in only 1/54 (1.85%) of neuroblastomas [6]. This contrasts sharply with the aforementioned studies, in which the prevalence of strong ALK immunohistochemical expression is generally around 50% or higher [2]–[5]. We were thus interested in comparing the performance of different antibodies.…”

Section: Introductionmentioning

confidence: 62%

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Platform Comparison for Evaluation of ALK Protein Immunohistochemical Expression, Genomic Copy Number and Hotspot Mutation Status in Neuroblastomas

et al. 2014

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ALK is an established causative oncogenic driver in neuroblastoma, and is likely to emerge as a routine biomarker in neuroblastoma diagnostics. At present, the optimal strategy for clinical diagnostic evaluation of ALK protein, genomic and hotspot mutation status is not well-studied. We evaluated ALK immunohistochemical (IHC) protein expression using three different antibodies (ALK1, 5A4 and D5F3 clones), ALK genomic status using single-color chromogenic in situ hybridization (CISH), and ALK hotspot mutation status using conventional Sanger sequencing and a next-generation sequencing platform (Ion Torrent Personal Genome Machine (IT-PGM)), in archival formalin-fixed, paraffin-embedded neuroblastoma samples. We found a significant difference in IHC results using the three different antibodies, with the highest percentage of positive cases seen on D5F3 immunohistochemistry. Correlation with ALK genomic and hotspot mutational status revealed that the majority of D5F3 ALK-positive cases did not possess either ALK genomic amplification or hotspot mutations. Comparison of sequencing platforms showed a perfect correlation between conventional Sanger and IT-PGM sequencing. Our findings suggest that D5F3 immunohistochemistry, single-color CISH and IT-PGM sequencing are suitable assays for evaluation of ALK status in future neuroblastoma clinical trials.

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Section: Introductionmentioning

confidence: 62%

“…ALK protein expression in neuroblastomas has been reported as an adverse prognostic factor by several groups [2]–[5]. At present, with regards to ascertainment of ALK immunohistochemical status, the major unresolved issue appears to be the choice of antibody, there being several available commercially (Table 1).…”

Section: Introductionmentioning

confidence: 99%

Platform Comparison for Evaluation of ALK Protein Immunohistochemical Expression, Genomic Copy Number and Hotspot Mutation Status in Neuroblastomas

et al. 2014

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“…35). ALK amplification is a common event in neuroblastoma and has recently been tied to poorer prognosis (36). This analysis reveals a clinically actionable combination that may provide a necessary therapeutic effect (37).…”

Section: Resultsmentioning

confidence: 99%

Harnessing Connectivity in a Large-Scale Small-Molecule Sensitivity Dataset

et al. 2015

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Identifying genetic alterations that prime a cancer cell to respond to a particular therapeutic agent can facilitate the development of precision cancer medicines. Cancer cell-line (CCL) profiling of small-molecule sensitivity has emerged as an unbiased method to assess the relationships between genetic or cellular features of CCLs and small-molecule response. Here, we developed annotated cluster multidimensional enrichment analysis to explore the associations between groups of small molecules and groups of CCLs in a new, quantitative sensitivity dataset. This analysis reveals insights into small-molecule mechanisms of action, and genomic features that associate with CCL response to small-molecule treatment. We are able to recapitulate known relationships between FDA-approved therapies and cancer dependencies and to uncover new relationships, including for KRAS-mutant cancers and neuroblastoma. To enable the cancer community to explore these data, and to generate novel hypotheses, we created an updated version of the Cancer Therapeutic Response Portal (CTRP v2).

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“…Wang et al [10] evaluated MYCN/ALK gene copy number by fluorescence in situ hybridization and detected ALK expression by IHC in 188 NB, 52 GNB, and 6 GN samples. Anaplastic lymphoma kinase positivity in NB (50.5%; 51/101) was significantly higher than that in GNB (22.6%; 7/31) and in GN (0.0%; 0/4).…”

Section: Discussionmentioning

confidence: 99%

Anaplastic lymphoma kinase gene expression in small round cell tumors of childhood—a comparative ımmunohistochemical study

Karakuş

Emir

Kaçar

et al. 2015

Annals of Diagnostic Pathology

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ALK amplification and protein expression predict inferior prognosis in neuroblastomas

Cited by 40 publications

References 22 publications

Platform Comparison for Evaluation of ALK Protein Immunohistochemical Expression, Genomic Copy Number and Hotspot Mutation Status in Neuroblastomas

Platform Comparison for Evaluation of ALK Protein Immunohistochemical Expression, Genomic Copy Number and Hotspot Mutation Status in Neuroblastomas

Harnessing Connectivity in a Large-Scale Small-Molecule Sensitivity Dataset

Anaplastic lymphoma kinase gene expression in small round cell tumors of childhood—a comparative ımmunohistochemical study

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