Laboratory for Molecular Pediatric Pathology (LaMPP)

Recent advances in molecular technology have vastly expanded the possibilities for personalized medicine. Benefiting from these techniques requires thoughtful test, coupled with a deep understanding of the clinical implications of molecular alterations. The promise of personalized medicine is to match specific aberrations in a patient’s tumor DNA to the most accurate diagnosis, the most up-to-date prognosis, and the most effective therapy available.

Many pediatric tumors and vascular malformations are defined by characteristic genetic changes that are best assessed by evolving molecular technologies. The correct diagnosis is essential to offering patients both the most accurate prognosis and the most effective therapy. To that end, we have designed a suite of molecular tests that will take the practice of diagnostic pediatric pathology to the next level with multiplex testing that delivers more actionable information with a better turnaround time.

The Boston Children’s Hospital Laboratory for Molecular Pediatric Pathology (BCH LaMPP) provides highly innovative tissue-based diagnostic testing uniquely tailored to serve pediatric patients, particularly those with cancer and developmental anomalies associated with tumor-like tissue overgrowths. The core technologies of the laboratory are focused on solid-state high throughput genomic sequencing, rare mutation detection and copy number analysis.

Next generation sequencing (NGS) technology is well-suited to the development of an assay to detect translocations that is both more successful and more informative than current tests. Typical DNA-based whole exome sequencing (WES) will not identify the majority of translocations because most translocation breakpoints are in introns rather than exons. RNA sequencing, however, is an ideal technique for detecting these translocations, because most pediatric solid tumor translocations create a fusion mRNA sequence that is highly expressed in the tumor. A targeted RNA sequencing panel will have many advantages: it will require relatively little starting material, will work with formalin-fixed, paraffin embedded tissue (FFPE), and will be able to detect both known and novel translocation partners. RNA-sequencing for translocations will require a novel informatics protocol to map the fused sequences.

Translocation detection is an essential part of solid tumor diagnostics in pediatric oncology. Many common childhood sarcomas, including Ewing sarcoma, synovial sarcoma, and alveolar rhabdomyosarcoma, among others, are defined by their translocations. The ability to accurately detect these translocations at the time of diagnosis is critical. We have designed a suite of molecular tests that will take the practice of diagnostic pediatric pathology to the next level with multiplex testing that delivers more actionable information with a better turnaround time. Each target will have the potential to alter the diagnosis, prognosis or therapy for our patients.