A mosaic PTEN mutation causing Cowden syndrome identified by deep sequencing.
Colin C Pritchard1, Christina Smith, Tatyana Marushchak
1Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA.
Summary
Deep sequencing identified a mosaic PTEN mutation in a Cowden syndrome patient, missed by standard methods. This highlights deep sequencing
Area of Science:
- Genetics
- Oncology
Background:
- Cowden syndrome is a rare genetic disorder associated with an increased risk of cancer.
- PTEN gene mutations are the primary cause of Cowden syndrome.
- Mosaic PTEN mutations, where only some cells carry the mutation, are not well characterized in this condition.
Observation:
- A 40-year-old woman with clinical Cowden syndrome, including Lhermitte-Duclos disease, was initially found to have no PTEN mutation via standard Sanger sequencing.
- Subsequent deep next-generation sequencing (NGS) using the ColoSeq assay detected a mosaic PTEN frameshift mutation (c.767_768delAG) at low levels (1.7%) in peripheral blood leukocytes.
Findings:
- The mosaic PTEN mutation was confirmed in various tissues, including skin fibroblasts, cerebellar tumor, colonic mucosa, and endocervical mucosa, at different levels.
- Deep NGS provided significantly higher sensitivity for detecting low-level mosaic mutations compared to conventional Sanger sequencing.
Implications:
- Deep NGS is crucial for diagnosing Cowden syndrome when traditional methods fail to detect low-level mosaic PTEN mutations.
- Mosaic PTEN mutations may be more prevalent in Cowden syndrome than previously recognized, necessitating advanced diagnostic approaches.
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