Oral Concurrent Session 7 - Basic and Translational Science
79 - Placental somatic mutation is associated with tissue infarction
Saturday, January 30, 2021
12:30 PM – 12:45 PM EST
Objective: Whether small-scale somatic mutation (single nucleotide and small insertion-deletion variants) is associated with placental dysfunction is unknown. Our goal was to explore genetic variation in relation to histopathologic findings suggestive of placental insufficiency using whole genome sequencing.
Study Design: This is a pilot case-control study. From the Stillbirth Collaborative Research Network, we identified 25 fetuses affected by varying degrees of placental insufficiency including healthy live births, growth restricted live births, and stillbirths due to placental insufficiency. Four frozen biopsies from every placenta and one frozen fetal tissue sample (brain or muscle) from each stillbirth underwent whole genome sequencing. Single nucleotide and insertion-deletion variants were called using the best practices workflow of the Genome Analysis Toolkit, and functional variants (moderate-high impact on protein product) were counted. Frozen placental samples had paired paraffin-embedded samples allowing for assessment of the relationship between somatic mutation rates and specific histology findings.
Results: We identified 25 eligible pregnancies (n=10 healthy live births, n=7 growth-restricted live births, and n=8 stillbirths) with a total of 100 placental samples. Median sequencing depth ranged from 20-38X for placental samples and 18-56X for fetal tissue samples. Considerable somatic variation was present in all placental samples. When restricted to mosaic variants present in a single biopsy and after accounting for total genome coverage, placental samples with diffuse infarcts had higher total and functional mutation rates than with no infarction (p=0.004, Table 1). While this relationship was not present among for other individual histological abnormalities, the mutation rates were higher if any abnormality was present (Table 2).
Conclusion: Somatic mutation was present in all placental samples, with highest mutation rates seen in samples with diffuse infarction. Somatic mutation may have a role in placental hypoxia and requires further study.