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Angiosarcoma : Molecular Genetics

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Angiosarcoma19_Breast_PostRadiation.jpg

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Molecular Genetics of Angiosarcoma (continued from the previous image): A recent study found CIC gene rearrangements and missense mutations in a subset of primary angiosarcomas (about 10% of all cases). The cases had the following characteristics: younger patients (mean age at diagnosis 41 years), solid growth pattern, epithelioid morphology, no identifiable vascular spaces, no history of radiation, and did not show MYC /FLT4 amplification.

CIC protein binds to target promoters and enhances and is a negative regulator of transcription. CIC-rearranged angiosarcomas show overexpression of PEA3 subfamily (ETV1, ETV4, ETV5) of ETS genes. ETS genes are one of the largest family of transcription factors involved in the regulation of cellular differentiation, cell cycle control, cell migration, cell proliferation, apoptosis, and angiogenesis. CIC gene abnormalities have been discovered in many cancers, including oligodendrogliomas, medulloblastoma, breast cancer, small round blue cell tumors, and now angiosarcomas.

The image from a post-radiation angiosarcoma of breast shows epithelioid morphology with large vesicular nuclei, prominent nucleoli, and intracytoplasmic lumina.

Reference: Huang, SC et al. Recurrent CIC Gene Abnormalities in Angiosarcoma : A Molecular Study of 120 Cases with Concurrent Investigation of PLCG1, KDR, MYC, and FLT4 Gene Alterations. Am J Surg Pathol. 2016 May; 40(5):645-655.

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