We have described the development and validation of a new gene-expression diagnostic test called Pheo-type for classification of PPGL tumors based on the underlying genetic driver of the disease. Our assay confirms that the predominant gene-expression subtypes of PPGL are closely linked to tumor genotype and for the first time show that classification can be achieved using a relatively small gene set. Pheo-type is similar to other clinical assays developed on the Nanostring platform for subtyping of solid tumors (50–52). As with these other studies, we have shown that robust gene-expression analysis can be achieved from small amounts of FFPE tissue material generating data that are comparable to other gene-expression platforms. The assay is rapid, largely automated, and cost effective, enabling the generation of results in 2 days from RNA extraction to data analysis, facilitating its implementation in a routine diagnostic laboratory.
2 Matching Annotations
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whereas a 32-year-old brother (III-3) presented with cerebellar HB, right eye retinal HB (Fig. 2b,c), renal cell carcinoma and pheochromocytoma.
PatientID: III-3
KindredID: 1
Case: M, 32Y0M, Mexican
DiseaseAssertion: VHL
FamilyInfo: Family composed of six affected individuals and three diseased subjects (III-2, III-3, III-4) were studied. III-4 (proband) presented with a CNS hemangioblastoma and a retinal hemangioblastoma. The mother (II-1) developed cerebellar, medullar and bilateral retinal HBs; two maternal aunts (II-2 and II-3) were affected by retinal and CNS HBs and unspecified renal tumors, whereas his grandfather (I-2) had unspecified abdominal tumors. All these relatives died in their early 30s. A 35-year-old sister (III-2) demonstrated cerebellar HB, right eye retinal HB and renal cell carcinoma, whereas a 32-year-old brother (III-3) presented with cerebellar HB, right eye retinal HB, renal cell carcinoma and pheochromocytoma. A mutation-carrier nephew (IV-2) presented only atrophy of the retinal pigment epithelium. All of these family members were found to have the R82P (c.245G>C) germline VHL variant. Eighteen additional healthy relatives were analyzed and tested negative for the mutation.
CohortInfo: Two families and one apparently non-familial case were studied at the Institute of Ophthalmology ‘Conde de Valenciana’ (Mexico City, Mexico).
CasePresentingHPOs: HP:0006880; HP:0009711; HP:0005584; HP:0002666 (Cerebellar hemangioblastoma, Retinal capillary hemangioma, Renal cell carcinoma, Pheochromocytoma)
CaseHPOFreeText: Cerebellar HB, right eye retinal HB, renal cell carcinoma and pheochromocytoma.
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CasePreviousTesting: N/A
PreviouslyPublished: N/A
SupplementalData: Family pedigree (Figure 1 (a))
Variant: p.R82P (c.245G>C)
LegacyVariant: N/A
CaseProblemVariantFreeText: N/A
ClinVarID: 526675, https://www.ncbi.nlm.nih.gov/clinvar/variation/526675/
CAID: N/A
gnomAD: N/A
VariantEvidence: N/A
MutationType: missense_variant;transversion
CivicName: R82P (c.245G>C)
MultipleGeneVariants: N/A
Tags
- ClinVarID:Yes
- Mutation:Germline
- DiseaseEntity:renalcellcarcinoma
- ClinVarID:526675
- Familial
- DiseaseEntity:pheochromocytoma
- AssumedRefSeq:NM_000551.3
- DiseaseEntity:cerebellarhemangioblastoma
- AminoAcidChange:ARGtoPRO
- cDNAposition:245
- inferred_gene_hgnc:7583
- FamilyPedigree
- CivicName:R82P(c.245G>C)
- MutationType:missense_variant;transversion
- DiseaseEntity:VHL
- inferred_gene_source:ClinVar
- InheritancePattern:AutosomalDominant
- Ethnicity:Mexican
- ProteinPosition:82
- DiseaseEntity:retinalcapillaryhemangioma
- VHL Hypothesis Annotation
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