Specialty Genomic Tests

Haemato-Oncology

Within the HaemOnc test directory a number of rare diagnostic tests will be delivered by specified GLHs as part of a national network.

Where these tests are not completed within our GLH, please refer samples via your local SIHMDS where they will be appropriately routed to the agreed and appropriate GLH within the national network.

Tests that will be routed outside of the GLH include:

  • t(15;17) MRD testing
  • Rare non-standard breakpoint cases of t(8;21) and inv(16) for MRD testing
  • Rare NPM1 transcript MRD testing
  • FIP1L1/PDGFRA MRD testing
  • Rare BCR/ABL1 MRD testing
Those rare tests delivered within the NE&Y GLH as part of this national network are shown below:

Histiocytosis Service:

The Newcastle Histiocytosis Service is led by Prof Matt Collin, Chair of the National Histiocytosis Advisory Group.   The Newcastle team also manage the UK Histiocytosis Registry (funded by Histio UK and CRUK).

Histiocytic disorders are a diverse group of rare neoplasms caused by somatic mutation and fusions of MAP kinase genes in cells of the macrophage/dendritic cell lineage.

The clinical entities include:

  • Langerhans cell histiocytosis,
  • Erdheim Chester disease,
  • Rosai Dorfman Destombes disease
  • Juvenile Xanthogranuloma
  • Indeterminate cell histiocytosis

Why is testing useful?

The clinical indications for genotyping in histiocytosis are:

  • BRAF inhibitors are highly effective for BRAF V600E-mutated disease
  • MEK inhibitors work for many BRAF-wild-type patients (depending upon the exact mutation)
  • Other kinase mutations are also directly targetable by an increasing array of small molecules.
  • Genotyping also has prognostic implications for risk of progression and neurological sequelae.

Genomic changes and testing

Clinically significant variants and fusions have been described in up to 90% of cases with histiocytic disorders.  About two-thirds of all cases have the BRAF V600E mutation that is detectable using a sensitive allele-specific PCR test.

The remainder of cases include BRAF and MAP2K1 insertion-deletion mutations (indels), mutations of CSF1R, RAS, PIK3CA, ARAF, MAP2K2, JAK3, KIT and fusions of BRAF, NTRK1, ALK and RET that require targeted NGS analysis.

Histiocytosis Service

In order to detect the spectrum of genetic abnormalities in histiocytic disorders, we offer a multi-component service:

  1. Highly sensitive targeted BRAF assay (allele specific PCR)
  2. 13 gene NGS panel (sub panel of paediatric NGS panel)
  3. RNA fusion panel

Samples required

Frozen Fresh tissue is recommended where possible.

FFPE: send two separate samples –
5x 10uM curls for DNA extraction (for BRAF and NGS panel testing) and
5x 10uM curls for RNA extraction (for RNA fusion panel testing) with a stated tumour cell content.

MRD in paediatric ALL is completed in small number of centres (including Sheffield) in the UK. This testing is extensive and bespoke and adheres to strict quality control measures set by the Euro MRD group.

NHS England are keen that the distribution of ALL MRD testing fits the geography associated with the GLHs. This has involved a process of repatriation of cases from the Newcastle and Leeds region to Sheffield which began in March 2020 and was completed in December 2020. A small number of cases from Nottingham and Leicester we managed through the Sheffield service, but have also now been repatriated to the service associated with the East GLH.

Currently, discussion are underway as to what the process will be for the adult ALL MRD testing and whether this will follow a similar pathway to the paediatric MRD or whether a centralised process will be available.

The AML MRD testing includes the common NPM1 changes (types A, B & D) and t(8;21) and inv(16). These tests have been validated in Leeds in order to comply with the repatriation and consolidation requirements of these tests to the NE&Y GLH.

Genomic Multi-Disciplinary Team Meetings

In order to support the interpretation of genomic data and its integration within the clinical Multi-Disciplinary Team process a series of genomic advisory boards have been established.

These are multi-disciplinary teams who analyse the more complex genomic results which arise from testing for larger numbers of gene abnormalities.

GMT Meetings

National Genomic Test Directory

The 2020/2021 National Genomic Test Directory for rare and inherited disorders and cancer.

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Genomic Laboratory Hub Services