High‐resolution melting and immunohistochemical analysis efficiently detects mutually exclusive genetic alterations of adamantinomatous and papillary craniopharyngiomas

Yoshimoto, Koji; Hatae, Ryusuke; Suzuki, Satoshi; Hata, Nobuhiro; Kuga, Daisuke; Akagi, Yojiro; Amemiya, Takeo; Sangatsuda, Yuhei; Mukae, Nobutaka; Mizoguchi, Masahiro; Iwaki, Toru; Iihara, Koji

doi:10.1111/neup.12408

Cited by 18 publications

(9 citation statements)

References 40 publications

(120 reference statements)

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“…11,12 Several recent studies have shown that CTNNB1 and BRAF (V600E) mutations were mutually exclusive for ACP and PCP tumors. 13,14 In the majority of ACP tumors, somatic mutations in exon 3 of CTNNB1 prevents degradation of β-catenin protein, thus activating the Wnt signaling, 15,16 whereas mutations in BRAF exon 15 in PCP tumors lead to MAP kinase pathway activation. 17 This discovery of specific mutations became useful to distinguish between ACP and PCP, and leading to the development of novel targeted therapies for patients with BRAF mutations in PCP cases.…”

Section: Introductionmentioning

confidence: 99%

<p>Adamantinomatous Craniopharyngioma in an Adult: A Case Report with NGS Analysis</p>

Jastania¹,

Saeed²,

Alkhalidi³

et al. 2020

IMCRJ

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Purpose: Several recent studies have documented CTNNB1 and BRAF mutations which are mutually exclusive for adamantinomatous craniopharyngioma (ACP) and papillary craniopharyngioma (PCP) tumors. This discovery is helpful in the development of novel targeted therapies in successful clinical trials with BRAF mutations in PCP cases. However, no such targeted therapy is available yet for ACP. Here, we report novel mutations, which are not previously reported, in a case of an adult ACP using NGS analysis. Results: Patient DNA was sequenced using Ion PI v3 chip on Ion Proton. A total of 16 variants were identified in this tumor by NGS analysis, out of which four were missense mutations, seven were synonymous mutations, and five were intronic variants. In CTNNB1 gene a known missense mutation in c.101G>T; in TP53 a known missense mutation in c.215C>G; and two known missense variants in PIK3CA, viz., in c.1173A>G; in exon 7, and in c.3128T>C; in exon 21, were found, respectively. Seven synonymous mutations were detected in this tumor, viz., in IDH1 (rs11554137), in FGFR3 (rs7688609), in PDGFRA (rs1873778), in APC (COSM3760869), in EGFR (rs1050171), in MET (rs35775721), and in RET (rs1800861), respectively. Three known, intronic variants were found in genes, such as PIK3CA, KDR, and JAK3, respectively. Also, a 3'-UTR and a splice site acceptor site variant in CSF1R and FLT3 genes were found in this tumor. We have shown allele coverage, allele ratio, and p-value, for all these mutations. The p-values and Phred quality score were significantly high for these variants. Conclusion: As reported in previous studies, in ACP tumors we found a CTNNB1 mutation by NGS analysis. The PIK3CA variants we detected were not known previously in ACP tumors. Finding the PIK3CA mutations in the ACP tumors may help develop targeted therapy for a subset of craniopharyngiomas with PIK3CA activating mutations. Clinical trials are in progress with specific PIK3CA inhibitors in advanced stages of many cancers.

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Section: Introductionmentioning

confidence: 99%

<p>Adamantinomatous Craniopharyngioma in an Adult: A Case Report with NGS Analysis</p>

Jastania¹,

Saeed²,

Alkhalidi³

et al. 2020

IMCRJ

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“…Adamantinomatous craniopharyngiomas (adaCP), a subtype of rare epithelial tumors, craniopharyngiomas, accounts for 5.6% to 15% of intracranial tumors and occurs in both children and young people . Although the histopathological classification of adaCP was considered as benign epithelial tumor, due to the complicated and important anatomical relationships around the tumor (such as optic nerve, optic chiasma, pituitary stalk, internal carotid artery, anterior cerebral artery, middle cerebral artery and other arteriae perforantes, the pituitary gland, hypothalamus, etc) and the factors of tumor own (such as parts, calcification, extent, adhesion, etc), total surgical excision rate of adaCP is low, the incidence of postoperative complications is high and serious, mortality, and disability rate are difficult to control .…”

Section: Introductionmentioning

confidence: 99%

CXCL12/CXCR4 promotes proliferation, migration, and invasion of adamantinomatous craniopharyngiomas via PI3K/AKT signal pathway

Yin

Liu

Zhu

et al. 2018

J of Cellular Biochemistry

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Objectives: Adamantinomatous craniopharyngiomas (adaCP) accounts for 5.6% to 15% of intracranial tumors. High expression of chemokine (C-X-C motif) ligand 12 (CXCL12, also known as stromal cell-derived factor 1 [SDF1]) and its receptor CXC receptor type 4 (CXCR4) are widespread in various malignancy via multiple signal transduction pathways. This study aims to investigate the mechanism of CXCL12/CXCR4 promoting proliferation, migration, and invasion of adaCP. Methods: Quantitative real-time polymerase chain reaction, Western blot analysis, and immunohistochemistry were used to evaluate the expression of CXCL12/CXCR4 mRNA and protein in 10 human adaCP tissues. Three successfully primary cell lines were obtained from native mainly solid tumor specimens, and confirmed by the means of inverted contrast microscope directly and following hematoxylin and eosin staining. Immunofluorescence was used to detect protein expression in vivo for the verification of primary cell line. Proliferation, migration, and invasion assays were performed to assess the biological functional role of CXCL12/CXCR4 in adaCP. The signal pathways involved in the action of CXCL12/CXCR4 in adaCP were also evaluated. Results: CXCL12 and CXCR4 were highly expressed in human adaCP samples.Primary adaCP cells were isolated and detected by the means of immunofluorescence for the detection of pan cytokeratin (pan-CK) and vimentin (VIM). Overexpression of CXCL12/CXCR4 significantly promoted the proliferation, migration, and invasion of primary adaCP cells. Moreover, cancer-promoting activity of CXCL12/CXCR4 is partially through its facilitation of PI3K/AKT signal pathway.Conclusions: Our data showed that CXCL12/CXCR4 promotes adaCP proliferation, migration, and invasion through PI3K/AKT signal pathway. These findings suggested that therapeutic strategies regulating CXCL12/CXCR4 expression may provide an effective treatment of adaCP. K E Y W O R D S adamantinomatous craniopharyngiomas, CXCL12/CXCR4, metastasis, PI3K/AKT, progression J Cell Biochem. 2019;120:9724-9736. wileyonlinelibrary.com/journal/jcb 9724 |

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“…Molecular detection of BRAF V600E mutation cannot yet be achieved in the prescribed time for intraoperative consultation (20-30 minutes). Rapid direct immunohistochemical methods are feasible but no study has tested the BRAF V600E antibody in the setting of craniopharyngioma intraoperative diagnosis (37)(38)(39). Figure 4 reports an algorithm proposed for intraoperative decision making.…”

Section: Discussionmentioning

confidence: 99%

Neoadjuvant B-RAF and MEK Inhibitor Targeted Therapy for Adult Papillary Craniopharyngiomas: A New Treatment Paradigm

et al. 2022

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BackgroundSurgical and clinical management of craniopharyngiomas is associated with high long-term morbidity especially in the case of hypothalamic involvement. Improvements in knowledge of craniopharyngioma molecular biology may offer the possibility of safe and effective medical neoadjuvant treatments in a subset of patients harboring papillary subtype tumors with a BRAFV600E mutation.MethodWe report herein two cases of tubero-infundibular and ventricular Papillary Craniopharyngiomas in which BRAF/MEK inhibitor combined therapy was used as adjuvant (Case 1) or neoadjuvant (Case 2) treatment, with a 90% reduction in tumor volume observed after only 5 months. In Case 2 the only surgical procedure used was a minimal invasive biopsy by the trans-ventricular neuroendoscopic approach. As a consequence, targeted therapy was administered in purely neoadjuvant fashion. After shrinkage of the tumor, both patients underwent fractionated radiotherapy on the small tumor remnant to achieve long-term tumor control. A review of a previously reported case has also been performed.ResultThis approach led to tumor control with minimal long-term morbidity in both cases. No side effects or complications were reported after medical treatment and adjuvant radiotherapy.ConclusionOur experience and a review of the literature argue for a change in the current treatment paradigm for Craniopharyngiomas (CPs). In giant and invasive tumors, confirmation of BRAFV600E mutated PCPs by biopsy and BRAF/MEK inhibitor therapy before proposing other treatments may be useful to improve long term outcomes for patients.

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High‐resolution melting and immunohistochemical analysis efficiently detects mutually exclusive genetic alterations of adamantinomatous and papillary craniopharyngiomas

Cited by 18 publications

References 40 publications

<p>Adamantinomatous Craniopharyngioma in an Adult: A Case Report with NGS Analysis</p>

<p>Adamantinomatous Craniopharyngioma in an Adult: A Case Report with NGS Analysis</p>

CXCL12/CXCR4 promotes proliferation, migration, and invasion of adamantinomatous craniopharyngiomas via PI3K/AKT signal pathway

Neoadjuvant B-RAF and MEK Inhibitor Targeted Therapy for Adult Papillary Craniopharyngiomas: A New Treatment Paradigm

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