Homozygous FANCM variant c.5101C>T p.(Gln1701*) in a patient
with early onset breast cancer, chemotherapy toxicity, and chromosome
fragility
- Sonja Sulkava,
- Anna H. Hakonen,
- Minna Pöyhönen,
- Heli Nevanlinna
Sonja Sulkava
Helsingin yliopisto
Corresponding Author:sonja.sulkava@thl.fi
Author ProfileAbstract
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Background Biallelic FANCM variants are linked to a Fanconi
anemia-like cancer predisposition syndrome which includes early onset
breast cancer, chemotherapy toxicity and chromosome fragility.
Additionally, heterozygous truncating variants have been linked to
increased breast cancer risk. However, the published results have been
inconsistent, and the risks and the functional effects associated with
the variants also vary depending on the position in the gene, with
N-terminal truncating variants having a stronger effect. Compared to
other FANCM variants studied, milder patient phenotypes and only
late onset breast cancer have been reported for the homozygous
C-terminal c.5101C>T variant, which is enriched in Finland.
Case We report here a Finnish patient, homozygous for the FANCM
c.5101C>T, p.(Gln1701*) variant, who manifested with early
onset triple negative breast cancer, chemotherapy toxicity and
chromosome fragility. The homozygous c.5101C>T has
previously been reported in two Finnish siblings with primary ovarian
insufficiency and chromosome fragility. Conclusion These findings
suggest that the C-terminal FANCM variant c. 5101C>T
may also cause a phenotype similar to the phenotype caused by N-terminal
truncating variants, when inherited in a homozygous state.20 Apr 2024Submitted to Cancer Reports 26 Apr 2024Reviewer(s) Assigned
19 Jul 2024Review(s) Completed, Editorial Evaluation Pending
24 Jul 2024Editorial Decision: Revise Major
13 Aug 20241st Revision Received
14 Aug 2024Assigned to Editor
14 Aug 2024Submission Checks Completed
14 Aug 2024Review(s) Completed, Editorial Evaluation Pending
19 Aug 2024Reviewer(s) Assigned
21 Oct 2024Editorial Decision: Revise Minor