| Autor: |
Krohn, Antje, Freudenthaler, Fabian, Harasimowicz, Silvia, Kluth, Martina, Fuchs, Sarah, Burkhardt, Lia, Stahl, Phillip, C Tsourlakis, Maria, Bauer, Melanie, Tennstedt, Pierre, Graefen, Markus, Steurer, Stefan, Sirma, Hueseyin, Sauter, Guido, Schlomm, Thorsten, Simon, Ronald, Minner, Sarah |
| Zdroj: |
Modern Pathology; December 2014, Vol. 27 Issue: 12 p1612-1620, 9p |
| Abstrakt: |
TMPRSS2:ERGfusions, in combination with deletion of the phosphatase and tensin homolog (PTEN) tumor suppressor, have been suggested to cooperatively drive tumor progression in prostate cancer. We utilized a novel heterogeneity tissue microarray containing samples from 10 different tumor blocks of 189 prostatectomy specimens to study heterogeneity of genomic PTENalterations in individual foci. PTENalterations were found in 48/123 (39%) analyzable individual tumor foci, including 40 foci with deletions, 7 with deletion and rearrangement, and 1 focus with rearrangement only. PTENwas homogeneously aberrant in only 4 (8%) and heterogeneously in 44 (92%) of the foci. We found a specific sequence of molecular events from PTENbreakage followed by deletion of DNA sequences flanking the breakpoint, resulting in homozygous deletion. The observation that 16 of 19 foci with homogeneous ERGpositivity had focal PTENalterations but none of 10 foci with PTENalterations had focal ERGpositivity (P<0.0001) suggests that PTENalterations typically develop subsequent to ERGfusions. We demonstrate a high level of intratumoral heterogeneity of PTENalterations with deletions and rearrangements that challenges potential PTENroutine diagnosis testing in biopsies. The observation that PTENalterations develop subsequent to ERGfusion strongly suggests that ERGexpression may directly drive development of PTENaberrations. |
| Databáze: |
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