Intragenic EGFR::EGFR.E1E8 Fusion (EGFRvIII) in 4331 Solid Tumors

Authors

Lan Zheng
Rajyalakshmi Luthra
Hector A Alvarez
F Anthony San Lucas
Dzifa Y Duose
Ignacio I Wistuba
Gregory N Fuller
Leomar Y Ballester
Sinchita Roy-Chowdhuri
Keith J Sweeney
Asif Rashid
Richard K Yang
Wei Chen
Audrey Liu
Yun Wu
Constance Albarracin
Keyur P Patel
Mark J Routbort
Aysegul A Sahin
Qingqing Ding
Hui Chen

Publication Date

12-19-2023

Journal

Cancers

Abstract

Simple Summary

Epidermal growth factor receptor variant III (EGFRvIII) is caused by the deletion of six exons and the fusion of exons 1 to exon 8. EGFRvIII occurs frequently in glioblastoma, a type of high-grade brain tumor; however, its presence in other solid tumors is not well characterized. Upon reviewing 4331 solid tumor cases tested via the 610-gene sequencing platform, EGFRvIII was identified in 17 cases, including 16 brain tumors and one breast tumor. EGFRvIII-positive brain tumors were all glioblastoma with wild-type IDH1/2 status, most with EGFR amplification and EGFR mutation. The only EGFRvIII-positive breast lesion was in a young female patient. A separate breast case tested outside our institution with reported EGFRvIII was noted in a young female patient. Both EGFRvIII-positive breast tumors showed high-grade sarcomatoid morphology. In summary, EGFRvIII is rare, occurring primarily in glioblastoma and rarely in breast sarcomatoid neoplasm. This select group of patients may benefit from chemotherapy and/or targeted anti-EGFR therapy.

Abstract

Epidermal growth factor receptor variant III (EGFRvIII, the deletion of exons 2–7) is a recurrent intragenic EGFR::EGFR.E1E8 fusion that occurs in high-grade gliomas. The presence of EGFRvIII in other solid tumors has not been well characterized. We retrospectively reviewed advanced malignant solid tumor cases tested by a custom hybrid capture 610-gene next-generation sequencing platform from 2021 to 2022. EGFRvIII was identified in 17 of 4331 (0.4%) cases, including 16 of 238 (7%) brain tumors and 1/301 (0.3%) breast tumors. EGFRvIII-positive brain tumors were all glioblastoma IDH-wildtype, most with concurrent TERT promoter mutation (14 of 16), EGFR amplification (13 of 16), and EGFR mutation (8 of 16). The only EGFRvIII-positive breast lesion was a sarcomatoid neoplasm in a young female patient. A separate breast case tested outside our institution with reported EGFRvIII was noted in a young female patient with a malignant phyllodes tumor with stromal overgrowth. Microscopically, both EGFRvIII-positive breast tumors showed high-grade sarcomatoid morphology with brisk mitotic activity. In summary, EGFRvIII is rare, occurring primarily in glioblastoma and rarely in breast sarcomatoid neoplasm, with no instances identified in other tumor types in our series. This select group of patients may benefit from chemotherapy and/or targeted anti-EGFR therapy.

Keywords

EGFRvIII, EGFR::EGFR.E1E8 fusion, glioblastoma, breast sarcomatoid neoplasm, malignant phyllodes tumor

DOI

10.3390/cancers16010006

PMID

38201434

PMCID

PMC10778229

PubMedCentral® Posted Date

12-19-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes