c-Kit gene mutations in intracranial germ cell tumors

Abstract Intracranial germ cell tumors (IGCTs) account for 3% of CNS tumors in children in the U.S. and 11% in Japan and East Asian countries. IGCTs are separated into two distinct subtypes based on histology: germinomas and non-germinomatous germ cell tumors (NGGCTs). The deep central location of IGCTs makes surgical resection and therefore molecular subtype classification difficult, and previous gene expression studies are limited. We performed mRNA expression profiling (Human Genome U133 Plus 2.0) and microRNA expression profiling (ABI TaqMan) with 36 and 49 IGCTs, respectively. Sample stratification using non-negative matrix factorization clustering of gene expression revealed two distinct subgroups that delineated germinomas from NGGCTs. Employing stepwise model building in each data set separately, we were able to separate these groups using only mRNA probes for the LIN28B and L1TD1 genes, and two microRNA, microRNA-26a and microRNA-373. MicroRNA26a suppresses the LIN28B gene and is down-regulated in germinoma. LIN28B directly binds and suppresses the let-7 microRNA family, which suppress the KRAS oncogene, previously found to be mutated in ~19% of IGCTs. L1TD1 is required for human stem cell renewal and directly interacts with LIN28B for its RNA binding function. LIN28B and L1TD1 are both known to be upregulated in other systemic germ cell tumors, but this has not yet been documented in IGCTs. In conclusion, these results show that intracranial germinomas have similar gene expression compared to systemic seminoma, and suggest a mechanism by which activation of LIN28B and L1TD1 downregulates the let-7 microRNA and subsequently upregulates KRAS.

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GCT-69. VOLUMETRIC CHANGE BEFORE CHEMORADIOTHERAPY AND INFLUENCE OF DIAGNOSTIC RADIATION EXPOSURE IN INTRACRANIAL GERMINOMAS

Neuro-Oncology ◽

10.1093/neuonc/noaa222.285 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii342-iii342

Author(s):

Naoki Kagawa ◽

Ryuichi Hirayama ◽

Chisato Yokota ◽

Yasuyoshi Chiba ◽

Yasunori Fujimoto ◽

...

Keyword(s):

Radiation Dose ◽

Germ Cell ◽

Tumor Volume ◽

Disease Onset ◽

Germ Cell Tumors ◽

Tumor Shrinkage ◽

Volumetric Change ◽

Volumetric Assessment ◽

Intracranial Germ Cell Tumors ◽

Diagnostic Radiation

Abstract BACKGROUND Spontaneous regression in intracranial germ cell tumors has been reported in some literatures, but the mechanism has not been well known. We retrospectively measured the tumor volume before chemoradiotherapy and analyzed factors that influence reduction of tumor volume. PATIENTS AND METHODS Plural MRI scans were done before the first course of chemotherapy regimen in 27 patients with primary intracranial germinomas. Their age ranged from 8 to 31 years. 35 lesions from them were enrolled and included 13 pineal, 4 neurohypophyseal, 4 basal ganglia, 4 bifocal type, and 2 multiple lesions. All regions were verified as pure germinoma or HCG-producing germinoma by histopathological examination. Tumor volume of 35 lesions was analyzed by volumetric assessment based on MRI. Ratio of volumetric change between the first MRI and the scan immediately before chemotherapy was defined as shrinking rate (%). Period between disease onset and the first chemotherapy was 20 to 47 days. Diagnostic radiation dose was calculated in each case. RESULTS Initial tumor volume ranged from 0.962 to 72.356 cubic centimeters (mean: 8.27). Diagnostic radiation dose: 40.5 to 910.1 mGy. Shrinking rate ranged from -57.8 to 85.4% (mean: 30.8). In 10 regions, shrinking rate was within 30%. Shrinking rate was significant positively influenced by diagnostic radiation dose (p<0.05) and negatively influenced by initial volume (p<0.05). But, other factors such as age, sex, histopathological parameters did not influence tumor shrinkage. CONCLUSION This study shows that the volume of intracranial germ cell tumors is changing dynamically before chemoradiotherapy in many cases. Diagnostic exposure to low-dose radiation influences tumor shrinkage of intracranial germinomas.

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GCT-30. TREATMENT OF PRIMARY INTRACRANIAL GERM CELL TUMORS: SINGLE INSTITUTION EXPERIENCE OF 74 CASES WITHOUT HISTOLOGICAL CONFIRMATION

Neuro-Oncology ◽

10.1093/neuonc/noaa222.250 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii334-iii334

Author(s):

Chengcheng Guo ◽

Qunying Yang ◽

Jian Wang ◽

Yonggao Mou ◽

Zhongping Chen

Keyword(s):

Germ Cell ◽

Tumor Therapy ◽

Survival Rates ◽

Gamma Knife Radiosurgery ◽

Germ Cell Tumors ◽

Cancer Center ◽

Chemotherapy Group ◽

Tumor Group ◽

Intracranial Germ Cell Tumors ◽

Histological Confirmation

Abstract BACKGROUND AND OBJECTIVE Primary intracranial germ cell tumors (PIGCTs) are a group of heterogeneous tumors. It is very difficult to treat those patients without pathological diagnosis. This study retrospectively analyzed the clinical data and outcomes of patients with clinically diagnosed (without histologically confirmed) PIGCTs in SunYat-sen University Cancer Center. METHODS Patients who were clinically diagnosed as PIGCTs without histological diagnosis through surgical resection or biopsy were included in this study. Patients were analyzed for clinical characteristics, treatment patterns, outcomes and adverse effects. RESULTS From May 2002 to July 2014, 74 patients clinically diagnosed with PIGCTs received chemotherapy and/or radiotherapy at the Sun Yat-sen University Cancer Center. The median age was 16.5 years old (4–45 years old, majority was teenagers). The most of tumors were found in male, and located in the pineal and suprasellar regions. When the patients were grouped into diagnostic chemotherapy group (57 cases), diagnostic radiotherapy group (5 cases) and gamma knife radiosurgery group (12 cases) based on their initial anti-tumor therapy. The 5-year survival rates were 84.3%, 75.0% and 75.0%, respectively. There was a trend that the chemotherapy group got a better survival. Patients were allocated to secretory tumor group (49 cases) and non-secretory tumor group (25 cases) based on their levels of tumor makers (α-FP and β-hCG). The 5- year survival rates were 80% and 77.8% (P value = 0.966), respectively. CONCLUSION Clinical diagnosed PIGCT (without histological confirmation) patients may obtain good responses when receiving comprehensive treatments of chemotherapy combined with radiotherapy.

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