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TERT Promoter Mutation c.-124C>T Commonly Occurs in Low-Grade Fibromatosis-like Metaplastic Breast Carcinoma.
- Source :
-
Archives of pathology & laboratory medicine [Arch Pathol Lab Med] 2023 Dec 01; Vol. 147 (12), pp. 1451-1457. - Publication Year :
- 2023
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Abstract
- Context.—: Low-grade fibromatosis-like metaplastic carcinoma (FLMC) is a very rare subtype of triple-negative metaplastic (spindle cell) breast carcinoma. It is characterized by the proliferation of spindle cells closely resembling fibromatosis, which represents a benign fibroblastic/myofibroblastic breast proliferation. Unlike most triple-negative and basal-like breast cancers, FLMC has a very low potential for metastases, but demonstrates frequent local recurrences.<br />Objective.—: To genetically characterize FLMC.<br />Design.—: To this end, we analyzed 7 cases by targeted next-generation sequencing for 315 cancer-related genes and performed comparative microarray copy number analysis in 5 of these cases.<br />Results.—: All cases shared TERT alterations (6 patients with recurrent c.-124C>T TERT promoter mutation and 1 patient with copy number gain encompassing the TERT locus), had oncogenic PIK3CA/PIK3R1 mutations (activation of the PI3K/AKT/mTOR pathway), and lacked mutations in TP53. TERT was overexpressed in all FLMCs. CDKN2A/B loss or mutation was observed in 4 of 7 cases (57%). Furthermore, tumors displayed chromosomal stability, with only few copy number variations and a low tumor mutational burden.<br />Conclusions—: We conclude that FLMCs typically show the recurrent TERT promoter mutation c.-124C>T, activation of the PI3K/AKT/mTOR pathway, low genomic instability, and wild-type TP53. In conjunction with previous data of metaplastic (spindle cell) carcinoma with and without fibromatosis-like morphology, FLMC is most likely distinguished by TERT promoter mutation. Thus, our data support the notion of a distinct subgroup within low-grade metaplastic breast cancer with spindle cell morphology and associated TERT mutations.<br /> (© 2023 College of American Pathologists.)
- Subjects :
- Humans
Female
DNA Copy Number Variations
Proto-Oncogene Proteins c-akt genetics
Phosphatidylinositol 3-Kinases genetics
TOR Serine-Threonine Kinases genetics
Mutation
Breast Neoplasms genetics
Breast Neoplasms pathology
Carcinoma pathology
Fibroma genetics
Fibroma pathology
Telomerase genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1543-2165
- Volume :
- 147
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Archives of pathology & laboratory medicine
- Publication Type :
- Academic Journal
- Accession number :
- 36897999
- Full Text :
- https://doi.org/10.5858/arpa.2022-0159-OA