The Impact of TSC-1 and -2 Mutations on Response to Therapy in Malignant PEComa: A Multicenter Retrospective Analysis.

Abstract

BACKGROUND:

Perivascular epithelioid cell neoplasms (PEComas) are a diverse family of mesenchymal tumors with myomelanocytic differentiation that disproportionately affect women and can be associated with tuberous sclerosis (TS). Although mTOR inhibition is widely used as first-line treatment, it is unclear what genomic alterations exist in these tumors and how they influence the response to therapy.

METHODS:

This was a multicenter study conducted at five sites within the US. The data were collected from 1 January 2004 to 31 January 2021. We conducted a retrospective analysis to identify PEComa patients with next-generation sequencing (NGS) data and compared outcomes based on mutations.

RESULTS:

No significant differences in survival were identified between TSC-1 and TSC-2 mutated PEComa or TSC-1/-2 versus other mutations. No significant difference was seen in progression-free survival (PFS) after first-line therapy between mTOR inhibition versus other systemic therapies.

CONCLUSIONS:

We were unable to detect differences in survival based on genomic alterations or PFS between mTOR inhibition versus other systemic therapies. Future studies should seek to identify other drivers of TSC-1/-2 silencing that could predict response to mTOR inhibition.

• Authors: Lawrence Liu, Carina Dehner, Nikhil Grandhi, Yang Lyu, Dana C Borcherding, John S A Chrisinger, Xiao Zhang, Jingqin Luo, Yu Tao, Amanda Parkes, Nam Q Bui, Elizabeth J Davis, Mohammed M Milhem, Varun Monga, Mia Weiss, Brian Van Tine, Angela C Hirbe
• Journal: Genes (Genes (Basel)) Vol. 13 Issue 11 (10 24 2022) ISSN: 2073-4425 [Electronic] Switzerland
• PMID: 36360169 (Publication Type: Multicenter Study, Journal Article)

Chemical References

• TOR Serine-Threonine Kinases

Topics

• Female
• Humans
• Mutation
• Perivascular Epithelioid Cell Neoplasms (genetics, pathology)
• Retrospective Studies
• TOR Serine-Threonine Kinases (genetics)