Integrated Multi-omic Analysis of Esthesioneuroblastomas Identifies Two Subgroups Linked to Cell Ontogeny

Classe, Marion; Yao, Hui; Mouawad, Roger; Creighton, Chad J.; Burgess, Alice; Allanic, Frederick; Wassef, Michel; Leroy, Xavier; Vérillaud, Benjamin; Mortuaire, G.; Bielle, Franck; Tourneau, Christophe Le; Kurtz, Jean Emmanuel; Khayat, David; Su, Xiaoping; Malouf, Gabriel G.

doi:10.1016/j.celrep.2018.09.047

Cited by 58 publications

(86 citation statements)

References 32 publications

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“…A recent study found that half of ENBs have clinically relevant genomic alteration, which are identified in different genes such as TP53 , PIK3CA , NF1 , CDKN2A , or CDKN2C . Recently, Classe et al reported an integrative multiomics analysis of ENB identifying two subgroups of ENBs: neural and basal . They showed that the basal‐like subgroup includes poorly differentiated tumors with a high expression of embryonic genes and a shorter survival for patients sharing some similarities with our cohort of pediatric ENBs (poor survival, dedifferentiated tumor, high Ki67).…”

Section: Discussionsupporting

confidence: 78%

“…They showed that the basal‐like subgroup includes poorly differentiated tumors with a high expression of embryonic genes and a shorter survival for patients sharing some similarities with our cohort of pediatric ENBs (poor survival, dedifferentiated tumor, high Ki67). Interestingly, basal‐like ENBs harbor IDH2 mutations in one‐third of cases that might represent a therapeutic option …”

Section: Discussionmentioning

confidence: 99%

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Pattern of loco‐regional relapses and treatment in pediatric esthesioneuroblastoma: The French very rare tumors group (Fracture) contribution

Dumont

Fresneau

Claude

et al. 2020

Pediatric Blood & Cancer

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Background Esthesioneuroblastoma (ENB) is a rare neuroectodermal tumor that seldom occurs during childhood. Multimodal treatments are currently proposed, but the place of each therapy is still in debate. Our objective is to describe clinical evolution, especially the pattern of relapses and determine contributors to tumor progression. Procedure Medical charts of all children (≤18 years) affected by ENB treated in France from January 1990 to December 2015 were retrospectively analyzed. Results Eighteen patients were selected (10 males). Median age at diagnosis was 12.2 years (0.9‐18). Tumor extension was Kadish stage A (n = 1), B (n = 3), C (n = 10), and D (n = 4). Hyams histological grades were I (n = 1), II (n = 3), III (n = 6), and IV (n = 6) (in two cases not defined). Initial cervical nodal spread was assessed by magnetic resonance imaging (n = 15), computed tomography scan (n = 16), fluorodeoxyglucose‐positron emission tomography‐computed tomography (n = 7), and cytological/histological analysis (n = 2). N1 stage was confirmed by imaging in two of 18 cases and one of two cases had cervical node dissection with neck irradiation (58 Gy). After a median follow‐up of survivors of 7.6 years (3.8‐17.9), 10 patients developed neuromeningeal progression, whereas no cervical nodal relapse occurred and only eight survived. Both 5‐year overall and event‐free survival rates were 44.4% (±11.7%). Conclusions The poor prognosis is mainly related to neuromeningeal dissemination that should be considered during treatment strategy. However, cervical lymph node relapse is rare.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Pattern of loco‐regional relapses and treatment in pediatric esthesioneuroblastoma: The French very rare tumors group (Fracture) contribution

Dumont

Fresneau

Claude

et al. 2020

Pediatric Blood & Cancer

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“…reported different mutational profiles in low‐grade and high‐grade ONBs, with no recurrent mutations in low‐grade ONBs, and IDH2 and TP53 mutations in higher‐grade ONBs. TP53 mutations have also been reported by others in high grade ONBs . It is possible that high‐grade tumours have a higher mutational load than low‐grade tumours, or have mutations that are more immunogenic.…”

Section: Discussionmentioning

confidence: 55%

“…This might be due to the stronger immunogenic profile of high‐grade tumours. The mutational landscape of ONBs is still poorly known . Classe et al .…”

Section: Discussionmentioning

confidence: 99%

Evaluating the prognostic potential of the Ki67 proliferation index and tumour‐infiltrating lymphocytes in olfactory neuroblastoma

Classe¹,

Burgess

Wassef³

et al. 2019

Histopathology

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Aims Olfactory neuroblastomas (ONBs) are rare malignant tumours that arise in the nasal vault. To date, the Hyams grade remains the only widely used histological grading system. However, it is based only on morphological criteria, and has not been updated since 1988. The objective of this study was to explore the prognostic potential of the Ki67 proliferation index (PI) and tumour‐infiltrating lymphocytes (TILs) in ONB. Methods and results A retrospective study was conducted on a bicentric series of 45 cases. The Ki67 PI was determined by counting at least 1000 nuclei on whole slides. TILs were evaluated with CD20, CD4 and CD8 immunohistochemical markers on whole slides. In this series, Hyams grades I, II, III and IV accounted for 13.4%, 44.4%, 20% and 22.2% of all cases, respectively. The Ki67 PI ranged from 1 to 93; the Ki67 PI was significantly higher in Hyams grade III–IV ONBs than in Hyams grade I–II ONBs (P < 0.0001). A Ki67 PI of ≥25 was associated with poorer survival (P = 0.02). TILs were present in both stromal and intratumoral compartments, but were located predominantly in the stromal component of the tumour. The numbers of intratumoral CD8+ cells/mm2 and CD4+ cells/mm2 were greater in high‐grade ONBs than in low‐grade ONBs (P = 0.0015 and P = 0.043, respectively). The numbers of T cells/mm2 and B cells/mm2 were not associated with survival, but a CD4/CD8 ratio of >2 was significantly associated with shorter survival (P = 0.04). Conclusion Our findings suggest that the Ki67 PI and TILs could be used as prognostic markers, as a potential alternative to the Hyams grade.

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“…This enabled researchers to identify molecular relationships between cancers, cluster prognostic variants and elucidate future therapeutic targets to explore. Furthermore, much of this anonymised data is publicly available on the Genomic Data Commons Data Portal for future research projects to utilise [146], and three non-TCGA cancer studies included in this review reported using this public data to overcome the rarity of their studied cancer type, to confirm cell ontology and even simply as a comparative control for their own gene expression data [69,70,99]. An additional point of interest was the computational algorithms used to overcome the statistical challenge of data integration in multi-omic studies of rare disease.…”

Section: Discussionmentioning

confidence: 99%

A scoping review and proposed workflow for multi-omic rare disease research

Kerr¹,

McAneney²,

Smyth³

et al. 2020

Orphanet J Rare Dis

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Background: Patients with rare diseases face unique challenges in obtaining a diagnosis, appropriate medical care and access to support services. Whole genome and exome sequencing have increased identification of causal variants compared to single gene testing alone, with diagnostic rates of approximately 50% for inherited diseases, however integrated multi-omic analysis may further increase diagnostic yield. Additionally, multi-omic analysis can aid the explanation of genotypic and phenotypic heterogeneity, which may not be evident from single omic analyses. Main body: This scoping review took a systematic approach to comprehensively search the electronic databases MEDLINE, EMBASE, PubMed, Web of Science, Scopus, Google Scholar, and the grey literature databases OpenGrey / GreyLit for journal articles pertaining to multi-omics and rare disease, written in English and published prior to the 30th December 2018. Additionally, The Cancer Genome Atlas publications were searched for relevant studies and forward citation searching / screening of reference lists was performed to identify further eligible articles. Following title, abstract and full text screening, 66 articles were found to be eligible for inclusion in this review. Of these 42 (64%) were studies of multi-omics and rare cancer, two (3%) were studies of multi-omics and a pre-cancerous condition, and 22 (33.3%) were studies of non-cancerous rare diseases. The average age of participants (where known) across studies was 39.4 years. There has been a significant increase in the number of multi-omic studies in recent years, with 66.7% of included studies conducted since 2016 and 33% since 2018. Fourteen combinations of multi-omic analyses for rare disease research were returned spanning genomics, epigenomics, transcriptomics, proteomics, phenomics and metabolomics. Conclusions: This scoping review emphasises the value of multi-omic analysis for rare disease research in several ways compared to single omic analysis, ranging from the provision of a diagnosis, identification of prognostic biomarkers, distinct molecular subtypes (particularly for rare cancers), and identification of novel therapeutic targets. Moving forward there is a critical need for collaboration of multi-omic rare disease studies to increase the potential to generate robust outcomes and development of standardised biorepository collection and reporting structures for multi-omic studies.

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Integrated Multi-omic Analysis of Esthesioneuroblastomas Identifies Two Subgroups Linked to Cell Ontogeny

Cited by 58 publications

References 32 publications

Pattern of loco‐regional relapses and treatment in pediatric esthesioneuroblastoma: The French very rare tumors group (Fracture) contribution

Pattern of loco‐regional relapses and treatment in pediatric esthesioneuroblastoma: The French very rare tumors group (Fracture) contribution

Evaluating the prognostic potential of the Ki67 proliferation index and tumour‐infiltrating lymphocytes in olfactory neuroblastoma

A scoping review and proposed workflow for multi-omic rare disease research

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