| Title: | Intronic Germline DICER1 Variants in Patients With Sertoli-Leydig Cell Tumor |
| Journal: | JCO Precision Oncology |
| Published: | 1 Sep 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37883719/ |
| DOI: | https://doi.org/10.1200/po.23.00189 |
| URL: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10860953 |
| Citations: | 5 (5 in last 2 years) as of 8 Aug 2024 |
Publication 9667
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Abstract
Germline pathogenic loss-of-function (pLOF) variants in DICER1 are associated with a predisposition for a variety of solid neoplasms, including pleuropulmonary blastoma and Sertoli-Leydig cell tumor (SLCT). The most common DICER1 pLOF variants include small insertions or deletions leading to frameshifts, and base substitutions leading to nonsense codons or altered splice sites. Larger deletions and pathogenic missense variants occur less frequently. Identifying these variants can trigger surveillance algorithms with potential for early detection of DICER1-related cancers and cascade testing of family members. However, some patients with DICER1-associated tumors have no pLOF variants detected by germline or tumor testing. Here, we present two patients with SLCT whose tumor sequencing showed only a somatic missense DICER1 RNase IIIb variant. Conventional exon-directed germline sequencing revealed no pLOF variants. Using a custom capture panel, we discovered novel intronic variants, ENST00000343455.7: c.1752+213A>G and c.1509+16A>G, that appear to interfere with normal splicing. We suggest that when no DICER1 pLOF variants or large deletions are discovered in exonic regions despite strong clinical suspicion, intron sequencing and splicing analysis should be performed.</p>
10 Keywords
- DEAD-box RNA Helicases
- Female
- Germ-Line Mutation
- Humans
- Introns
- Male
- Mutation
- Ovarian Neoplasms
- Ribonuclease III
- Sertoli-Leydig Cell Tumor
16 Authors
- Claudette R. Fraire
- Paige R. Mallinger
- Jessica N. Hatton
- Jung Kim
- David S. Dickens
- Peter A. Argenta
- Samuel Milanovich
- Taylor Hartshorne
- David J. Carey
- Jeremy S. Haley
- Gretchen Urban
- Jeon Lee
- D. Ashley Hill
- Douglas R. Stewart
- Kris Ann P. Schultz
- Kenneth S. Chen
1 Application
| Application ID | Title |
|---|---|
| 54389 | Frequency, phenotypic spectrum, and penetrance of pathogenic variation in cancer susceptibility genes in the general population |
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