TP53 structural variants in metastatic prostatic carcinoma

被引:14
作者
Sirohi, Deepika [1 ,2 ,3 ]
Devine, Patrick [1 ]
Grenert, James P. [1 ]
van Ziffle, Jessica [1 ]
Simko, Jeffry P. [1 ]
Stohr, Bradley A. [1 ]
机构
[1] Univ Calif San Francisco, Dept Pathol & Lab Med, San Francisco, CA 94143 USA
[2] Univ Utah, Dept Pathol, Salt Lake City, UT 84112 USA
[3] ARUP Labs, Salt Lake City, UT 84108 USA
关键词
P53; CANCER; EXPRESSION; REARRANGEMENTS; MUTATION;
D O I
10.1371/journal.pone.0218618
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Sequencing data have been instrumental in identifying oncogenic drivers in prostatic carcinoma and highlighting biomarkers that define aggressive disease. A review of a series of 30 primary and metastatic prostatic carcinomas clinically sequenced at our cancer genomics laboratory utilizing a targeted gene panel identified recurrent structural variants in the TP53 gene. These structural variants were found in 27% of all sequenced cases and represented 36% of the cases with metastatic disease. TP53 structural rearrangements have been previously reported in a significant subset of osteosarcomas, where they result in loss of p53 protein expression by immunohistochemistry. Similarly, in our prostate cases with TP53 structural rearrangements for which tissue was available for testing, we find loss of p53 protein expression by immunohistochemistry. In the eight TP53-rearranged cases, concurrent PTEN loss was identified in 4 cases, TMPRSS2-ERG fusion in 5 cases, and AR and FOXA1 amplification in 1 case each. Our results from this small case series suggest that TP53 rearrangements with loss of expression represent a frequent alternative mechanism of inactivation of this key tumor suppressor gene with potential utility as a marker of aggressive disease. Recognition of this TP53 rearrangement pathway is essential to accurately identify prostatic carcinomas with loss of TP53 function.
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页数:10
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