Article
PIK3CA somatic mutation in a patient with Aberrant Muscle Syndrome and Lymphatic Malformation
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Authors
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Jessica Steele
- Queen Victoria Hospital, East Grinstead, United Kingdom
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Tony Penington
- Royal Children's Hospital, Melbourne, Australia
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Michael Christie
- Centre for Translational Pathology, University of Melbourne, Melbourne, Australia
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Chris Coombs
- Royal Children's Hospital, Melbourne, Australia
| Published: | February 6, 2020 |
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Outline
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Objectives/Interrogation: Aberrant muscle syndrome (AMS), a rare congenital hand difference, is characterized by unilateral non-progressive muscular hyperplasia of the upper limb. PIK3CA is an upstream regulator of the AKT-mTOR cell signalling pathway, and activating mutations of this gene promote cell proliferation. Mutiple syndromes of overgrowth (CLOVES, FAO, Macrodactyly) have been found to have associated mutations of PIK3CA, and the umbrella term 'PIK3CA related overgrowth spectrum' (PROS) has been created to characterise this group of conditions.
Two cases of AMS with mutations of PIK3CA have previously been reported. We report the first case of a patient with AMS and a lymphatic malformation, both found to have the same mutation of PIK3CA.
Methods: Targeted next generation sequencing of DNA extracted from formalin fixed paraffin embedded (FFPE) slides was undertaken on both skeletal muscle affected by AMS and tissue from a lymphatic malformation of the chest wall in one patient. Regions of interest from exon 15 of the BRAF gene, exons 9 and 20 of the PIK3CA gene, exons 2, 3, and 4 of both KRAS and NRAS genes, and exons 18, 19, 20 and 21 of the EGFR gene were amplified using multiplex PCR. Sequencing was performed on an Illumina MiSeq Next Generation Sequencer, and mutations were detected using MiSeq Reporter software.
Results and Conclusions: In the skeletal muscle a PIK3CA E542K (c.1624G>A, exon 9) mutation was detected with a mutation allele fraction of 19%. The same PIK3CA E542K mutation was detected in the lymphatic malformation tissue at a much lower mutation allele fraction of 0.22%.
Five common PIK3CA mutation locations have been determined within the PIK3CA Related Overgrowth Spectrum (PROS). Our case and the previously reported AMS cases all have mutations among the five canonical PIK3CA mutations previously described. The fact that the same PIK3CA mutation has been found in multiple different tissue types suggests that this mutation arises in a cell that contributes to the development of several tissue types during embryogenesis. This is the first description of the same PIK3CA somatic mutation in a patient with both AMS and a lymphatic malformation. Our case extends the breadth of clinical presentations of patients with PIK3CA mutations.
