Additional genetic alterations in BRAF-mutant gliomas correlate with histologic diagnoses.
Recently, the term "Diffuse glioma, BRAF V600E-mutant" has been recommended for IDH-wildtype gliomas with BRAF p.V600E mutation and without CDKN2A/B deletion. However, additional alterations in gliomas that coexist with BRAF-mutations are poorly defined.
We analyzed next-generation sequencing results in 315 cancer-associated genes for 372 gliomas from our institution (2010 to 2017). In addition, we reviewed IDH-WT gliomas with mutation and copy-number alterations available in cBioPortal, to further characterize BRAF-mutant gliomas.
Seventeen (4.6%) showed BRAF mutations. Tumor types included 8 glioblastomas, 2 epithelioid glioblastomas (E-GBM), 2 pleomorphic xanthoastrocytomas (PXA), 1 anaplastic oligodendroglioma, 1 diffuse astrocytoma, and 3 pilocytic astrocytomas. Fifty-three percent (53%) of cases exhibited BRAF-alterations other than p.V600E. The majority of the tumors were localized in the temporal lobe (52.9%). In addition to BRAF mutations, glioblastomas showed concomitant mutations in TP53 (3/8), CDKN2A/B-loss (6/8), TERT-promoter (6/8), and/or PTEN (5/8). Both E-GBMs and PXAs showed CDKN2A/B-loss and BRAF p.V600E with absence of TERTp, TP53, and PTEN mutations. Similar findings were observed in BRAF-mutant infiltrating gliomas from cBioPortal.
Knowledge of additional alterations that co-occur with BRAF-mutations in gliomas may improve diagnosis and help identify patients that could benefit from targeted therapies. Furthermore, we provide examples of two patients whose tumors responded to BRAF pathway inhibitors, arguing in favor of these therapies in patients with BRAF-mutant gliomas.
Publication Date: 2020-10-04
Journal: Journal of neuro-oncology
Molecular Guided Treatments in Gynecologic Oncology: Analysis of a Real-World Precision Cancer Medicine Platform.
Advanced gynecologic cancers have a poor prognosis and constitute a major challenge for adequate treatment strategies. By analyzing and targeting molecular alterations, molecular guided treatments may be a viable option for the treatment of advanced gynecologic cancers.
In this single-center, real-world retrospective analysis of our platform for precision cancer medicine (PCM), we describe the molecular profiling of 72 patients diagnosed with different types of advanced gynecologic malignancies. Tumor samples of the patients were examined by next-generation sequencing panel and immunohistochemistry (IHC).
In total, we identified 209 genetic aberrations in 72 patients. The ten most frequent alterations were TP53 (n = 42, 20%), KRAS (n = 14, 6.6%), PIK3CA (n = 11, 5.2%), PIK3R1 (n = 9, 4.3%), ATR (n = 8, 3.8%), PTEN (n = 8, 3.8%), BRCA1 (n = 6, 2.8%), NF1 (n = 4, 1.9%), NOTCH1 (n = 4, 1.9%), and POLE (n = 4, 1.9%), which account for more than half of all molecular alterations (52.6%). In 21 (29.1%) patients only one mutation could be detected, and 44 (61.1%) patients had more than one mutation. No molecular alterations were detected in seven (9.7%) patients. IHC detected expression of phosphorylated mammalian target of rapamycin and epidermal growth factor receptor in 58 (80.6%) and 53 (73.6%) patients, respectively. In over two thirds (n = 49, 68.1%), a targeted therapy was suggested, based on the identified genetic aberrations. The most frequently recommended specific treatment was the combination of everolimus with exemestane (n = 18, 25 %).
Based on our observations, it seems that PCM might be a feasible approach for advanced gynecologic cancers with limited treatment options.
Nowadays molecular profiling of advanced gynecologic malignancies is feasible in the clinical routine. A molecular portrait should be done for every patient with an advanced therapy-refractory gynecologic malignancy to offer molecular-based treatment concepts.
Publication Date: 2020-05-06
Journal: The oncologist