Deletions in the 17q chromosomal region and their influence on the clonal cytogenetic evolution of recurrent meningiomas

Abstract

Objective Meningiomas are among the most frequent intracranial tumors. Although the majority of meningiomas can be cured by surgical resection, up to 20% of the patients develop an aggressive clinical course with tumor recurrence or progressive disease. Cytogenetically, meningiomas frequently harbour a normal karyotype or monosomy of chromosome 22 as the sole anomaly. However, progression of meningiomas is associated with a non-random pattern of secondary losses of the chromosomes and chromosomal regions 1p, 6, 10, 14, 18, and 19. There is evidence, that loss of chromosome 17 might be involved in the clonal cytogenetic evolution of recurrent meningiomas. The aim of this study was to determine the role of deletions in the 17q chromosomal region in patients with recurrent meningiomas. Results The authors retrospectively reviewed all patients that underwent repeated surgery for recurrent meningiomas between 1999 and 2015 at the Department of Neurosurgery of the Saarland University Hospital. Patients were included in this study if tumor samples from two or more different meningiomas were available. A total of 7 patients underwent repeated surgery for recurrent meningiomas (4 males, 3 females, mean age: 45.4 years at the date of surgery) between 1999 and 2015. Collectively, 22 biopsies were analyzed with FISH (fluorescence-in-situ-hybridization) for the chromosomal region 17q23.3. In 20/22 (90.1%) specimens, the tumor samples harboured a significant deletion in the chromosomal region 17q (range: 10 to 63% of the cells). In 3/3 (100%) cases, deletion in the 17q chromosomal region was detectable in the primary tumor. In the tumor evolution, there was no steady in- or decrease in the percentage of this deletion. Conclusion Deletion in the 17q chromosomal region was present in the patients’ primary tumors as well as in late recurrences. Overall, a significant deletion in the 17q chromosomal region was detected in 90.1% of the tumors. Thus, the authors assume that deletion in the 17q chromosomal region displays rather an early event in meningioma progression. Accordingly, deletion in the 17q chromosomal region might clinically serve as a potential early marker for malignancy and a higher risk for recurrence in meningiomas.

The integrated multiomic diagnosis of sporadic meningiomas: a review of its clinical implications

“…Other frequent CNVs include chromosome 9p deletion, which contains tumor suppressor genes Cyclin-Dependent Kinase Inhibitor 2A and 2B (CDKN2A/B) [15], and loss of chromosomes 2p, 4p, 6q, 7p, 9p, 10q, 11p, 14q, 17q, and 18q [29][30][31][32][33][34][35][36][37]. Chromosome 2p loss is associated with choroid meningiomas, while anaplastic meningiomas demonstrate chromosome 1p, 6p, 14, and 22q losses [15].…”

Identification of Clinical Candidate M2698, a Dual p70S6K and Akt Inhibitor, for Treatment of PAM Pathway-Altered Cancers

“…Most small substituents in the meta-and para-positions were well tolerated. Compared with the naked aryl ring, halogens (12,13), electronwithdrawing groups (15,16), and electron-donating groups (18,19) all led to potency improvements. However, orthosubstituted derivatives (11,14,17) all led to a decrease in potency.…”

“…The title compound was prepared using S6 to give the product as an offwhite solid (32 mg, 80.3%). 27 1 4-(4-Fluoro-benzylamino)-quinazoline-8-carboxamide (13). The title compound was prepared using S6 to give the product as an offwhite solid (28 mg, 78%).…”

“…p70S6K also has a unique signaling potential to phosphorylate several targets that influence protein translation, cellular survival, growth, and migration. The amplification of chromosomal locus 17q23, which contains the S6K1 gene, RPS6 KB1, is a feature of numerous cancers including meningioma 13 and breast cancer, 14 suggesting that S6K1 may participate in tumorigenesis independently of other targets of mTOR, making S6 kinase an attractive therapeutic target.…”

Bone Invasive Meningioma: Recent Advances and Therapeutic Perspectives

“…Most recently, technological developments have suggested that a higher rate of malignant meningiomas may be induced by increasing hypodiploidy, complex ablations, and even epigenetics (77)(78)(79)(80). Furthermore, certain characteristics have been correlated with histological subtypes, especially copy number alterations and mutations, suggesting a greater potential for gene therapy (58,80).…”