Detection and molecular monitoring of FIP1L1-PDGFRA-positive disease by analysis of patient-specific genomic DNA fusion junctions.
| Autor: | Score, J., Walz, C., Jovanovic, J. V., Jones, A. V., Waghorn, K., Hidalgo-Curtis, C., Lin, F., Grimwade, D., Grand, F., Reiter, A., Cross, N. C. P. |
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| Předmět: |
EOSINOPHIL disorders
SYNDROMES PATIENTS GENE fusion IMATINIB ANTINEOPLASTIC agents MEDICAL care PROTEIN analysis HYPEREOSINOPHILIC syndrome CARCINOGENESIS CELL receptors COMPARATIVE studies DNA probes GENES GENETICS HUMAN genome RESEARCH methodology MEDICAL cooperation POLYMERASE chain reaction PROTEINS RESEARCH EVALUATION research DIAGNOSIS |
| Zdroj: | Leukemia (08876924); Feb2009, Vol. 23 Issue 2, p332-339, 8p, 1 Black and White Photograph, 1 Diagram, 2 Charts, 4 Graphs |
| Abstrakt: | To evaluate current detection methods for FIP1L1-PDGFRA in hypereosinophilic syndrome (HES), we developed a means to rapidly amplify genomic break points. We screened 202 cases and detected genomic junctions in all samples previously identified as RT-PCR positive (n=43). Genomic fusions were amplified by single step PCR in all cases whereas only 22 (51%) were single step RT-PCR positive. Importantly, FIP1L1-PDGFRA was detected in two cases that initially tested negative by RT-PCR or fluorescence in situ hybridization. Absolute quantitation of the fusion by real-time PCR from genomic DNA (gDNA) using patient-specific primer/probe combinations at presentation (n=13) revealed a 40-fold variation between patients (range, 0.027-1.1 FIP1L1-PDGFRA copies/haploid genome). In follow up samples, quantitative analysis of gDNA gave 1-2 log greater sensitivity than RQ-PCR of cDNA. Minimal residual disease assessment using gDNA showed that 11 of 13 patients achieved complete molecular response to imatinib within a median of 9 months (range, 3-17) of starting treatment, with a sensitivity of detection of up to 1 in 10(5). One case relapsed with an acquired D842V mutation. We conclude that detection of FIP1L1-PDGFRA from gDNA is a useful adjunct to standard diagnostic procedures and enables more sensitive follow up of positive cases after treatment. [ABSTRACT FROM AUTHOR] |
| Databáze: | Complementary Index |
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