1. TERT Promoter Mutation c.-124C>T Commonly Occurs in Low-Grade Fibromatosis-like Metaplastic Breast Carcinoma
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Webersinke, Gerald, Burghofer, Jonathan, Malli, Theodora, Rammer, Melanie, Jahn, Stephan Wenzel, Niendorf, Axel, Tavassoli, Fattaneh A., and Moinfar, Farid
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Thermo Fisher Scientific Inc. ,Scientific equipment and supplies industry -- Genetic aspects -- Analysis ,Tumor proteins -- Development and progression -- Genetic aspects ,Genes -- Genetic aspects -- Analysis ,Metastasis -- Genetic aspects -- Development and progression ,Carcinoma -- Genetic aspects -- Development and progression ,Cancer -- Genetic aspects -- Development and progression ,Breast cancer -- Development and progression -- Genetic aspects ,Health - 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. Objective.--To genetically characterize FLMC. 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. 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. 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. (Arch Pathol Lab Med. 2023;147:1451-1457; doi: 10.5858/arpa.2022-0159-OA), Low-grade fibromatosis-like metaplastic carcinomas (FLMCs) are very rare tumors, comprising less than 0.5% of breast carcinomas. FLMCs are part of the heterogeneous group of metaplastic breast carcinomas (MBCs), characterized by [...]
- Published
- 2023
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