Comparison of Ion Personal Genome Machine Platforms for the Detection of Variants in BRCA1 and BRCA2 / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Transition to next generation sequencing (NGS) for BRCA1/BRCA2 analysis in clinical laboratories is ongoing but different platforms and/or data analysis pipelines give different results resulting in difficulties in implementation. We have evaluated the Ion Personal Genome Machine (PGM) Platforms (Ion PGM, Ion PGM Dx, Thermo Fisher Scientific) for the analysis of BRCA1/2. MATERIALS AND METHODS: The results of Ion PGM with OTG-snpcaller, a pipeline based on Torrent mapping alignment program and Genome Analysis Toolkit, from 75 clinical samples and 14 reference DNA samples were compared with Sanger sequencing for BRCA1/BRCA2. Ten clinical samples and 14 reference DNA samples were additionally sequenced by Ion PGM Dx with Torrent Suite. RESULTS: Fifty types of variants including 18 pathogenic or variants of unknown significance were identified from 75 clinical samples and known variants of the reference samples were confirmed by Sanger sequencing and/or NGS. One false-negative results were present for Ion PGM/OTG-snpcaller for an indel variant misidentified as a single nucleotide variant. However, eight discordant results were present for Ion PGM Dx/Torrent Suite with both false-positive and -negative results. A 40-bp deletion, a 4-bp deletion and a 1-bp deletion variant was not called and a false-positive deletion was identified. Four other variants were misidentified as another variant. CONCLUSION: Ion PGM/OTG-snpcaller showed acceptable performance with good concordance with Sanger sequencing. However, Ion PGM Dx/Torrent Suite showed many discrepant results not suitable for use in a clinical laboratory, requiring further optimization of the data analysis for calling variants.

Erratum: Prevalence of germline BRCA mutations among women with carcinoma of the peritoneum or fallopian tube / 부인종양

The original article contained errors.

Prevalence of germline BRCA mutations among women with carcinoma of the peritoneum or fallopian tube / 부인종양

OBJECTIVE: The aim of the present study was to assess the frequency of germline mutations in patients with peritoneal carcinoma (PC) or the fallopian tube carcinoma (FTC), using a multi-gene panel. METHODS: Twenty-six patients diagnosed with either PC or FTC between January 2013 and December 2016 were recruited consecutively. Germline DNA was sequenced using a 6-gene next generation sequencing (NGS) panel following genetic counseling. Surgico-medical information was obtained from hospital records. Genetic variations were detected using the panel and were cross-validated by Sanger direct sequencing. RESULTS: Germline BRCA1/2 mutations were identified in 6 patients (23.1%). Four were detected in patients with PC and 2 were in FTC patients. No mutations were detected in TP53, PTEN, CDH1, or PALB2. We identified 11 variant of uncertain significance (VUS) in 9 patients; 2 in BRCA1, 3 in BRCA2, 2 in TP53, and 4 in CDH1. We also detected a CDH1 c.2164+16->A VUS in 3 patients. CONCLUSION: The prevalence of germline BRCA1/2 mutations in patients with PC or FTC is comparable to that of BRCA1/2 mutations in epithelial ovarian cancer patients.

Late Solitary Cerebral Metastasis from Renal Cell Carcinoma 10 Years after Nephrectomy

We report a case of solitary brain metastasis from renal cell carcinoma 10 years after nephrectomy. A 71-year-old woman developed sudden onset of headache, dysarthria, gait disturbance and right hemiparesis. She previously had undergone a left nephrectomy due to renal cell carcinoma 10 years ago. A brain magnetic resonance image revealed a well defined round mass with massive peritumoral edema in the left occipital area, which was surgically removed completely. Microscopic appearances of the brain tumor were similar to those of the renal cell carcinoma or hemangioblastoma. Positive immunoreaction for epithelial membrane antigen and cytokeratin confirmed the diagnosis of metastatic renal cell carcinoma. In a review of the literature, ten cases of solitary brain metastasis of renal cell carcinoma with a latency period of more than 10 years after nephrectomy have been reported.

Evaluation of Cerebrospinal Fluid Vascular Endothelial Growth Factor for the Brain Tumor

OBJECTIVE: Vascular endothelial growth factor(VEGF), which is also known as vascular permeability factor, induces angiogenesis and may play a key role in tumor-related neovascularization and peritumoral edema. There are many pathological conditions associated with VEGF expression, such as brain tumor, infection and trauma. Malignant brain tumor is characterized by its prominent neovascularization and severe peritumoral edema and it is known to express high VEGF activity. The aim of this study is to investigate any differences in cerebrospinal fluid(CSF) VEGF level among gliomas, and between tumors and non-tumorous conditions. METHODS: Cerebrospinal fluid samples were collected from 28 patients whose diagnosis had been surgically proven and they were centrifuged and stored at -73 degrees C. The concentration of VEGF was analyzed using commercially available ELISA kit. RESULTS: Glioblastoma patients showed much higher level of CSF VEGF than those of other gliomas and non-tumorous conditions. And higher CSF VEGF level was found in invasive pituitary adenoma, recurrent oligoden-droglioma, central neurocytoma and diffuse axonal injury. CONCLUSION: Absolute CSF VEGF level can be useful biological marker for primary malignant glioma, especially glioblastoma, and serial check-ups may contribute to early diagnosis of malignant transformation of low grade astrocytoma.

Outcome of Postoperative Intratumoral Bleomycin Injection for Cystic Craniopharyngioma

Total excision is a treatment of choice in preventing the relapse of craniopharyn-gioma, but for tumors involving an extensive area, it is often associated with an increased risk of complications. We have performed a partial or subtotal tumor removal followed by repeated injection of bleomycin into the remaining tumor through a subcutaneous reservoir as postoperative adjuvant therapy. A retro-spective review of clinical, radiological, and surgical data was performed for 10 patients (5 males and 5 females; age, 3-65 yr; follow-up duration, 12-79 months) with cystic craniopharyngiomas. The measurements of lactate dehydrogenase (LDH) level at each aspiration were performed. The shrinkage and/or stabiliza-tion of tumor was initially noted in all cases. The recurrence of tumor was seen in 4 cases (40%). The decreased or increased level of LDH was interpreted as tumor shrinkage or recurrence, respectively. The transient toxic reactions were observed in 3 patients (30%). Our study demonstrates that postoperative bleo-mycin injection for cystic craniopharyngioma, although does not appear to eradi-cate the tumor, decreases and stabilizes the tumor size, when used as an adju-vant therapy in young patients.

Giant Cystic Craniopharyngioma Extended into the Posterior Fossa down to the Medulla Oblongata: Case Report

Cystic retrochiasmatic craniopharyngioma may reach enormous size by expanding into the posterior fossa along the retroclival area, which is very unusual finding. An 11-year-old girl presented with walking disturbance and irritability. On the neurological examination, she had positive Babinski sign, hyperactive deep tendon reflex, and left lateral gaze nystagmus. She also had right hearing disturbance. Initial magnetic resonance(MR) images revealed a huge, thin capsuled cystic mass which extended into the cerebellopontine angle down to the medulla oblongata. Secondary adjuvant chemotherapy, radiotherapy, and reoperation were necessary after first tumor removal by a suboccipital approach, due to the progression of disease. Finally, neurological condition was much improved without remnant tumor although some sequelae were remained. We report this interesting case because of its rarity, complex clinical presentation, and challenge in its management.

The Effect of Intraventricular Methotrexate in a Patient of Disseminated Anaplastic Oligodendroglioma: Case Report

Oligodendrogiomas account for about 4 per cent of intracranial gliomas and surgery is known to be an essential first step to establish an accurate diagnosis and when oligodendrogliomas recur with or without anaplastic features after initial resection, radiation and chemotherapy consisting of the administration of procarbazine, lomustine, and vincristine are usually indicated. We report our experience of an excellent result with intraventricular methotrexate chemotherapy for a patient with disseminated anaplastic oligodendroglioma. A 29-year-old male patient presented with diplopia and headache for two months. MRI showed a irregular, faintly enhanced mass in the posterior fossa. The hisotological diagnosis was an anaplaplastic oligodendroglioma and he was treated with chemotherapy of PCV regimen and radiotherapy followed by surgery. CSF dissemination was revealed by a follow-up MRI during the period. Intraventricular methotrexate(0.175mg/kg) was given twice a week for 4 weeks through ommaya reservoir and the size of the multiple tumors was decreased significantly on follow-up MRI. This case report suggests that an aggressive treatment involving intravent-ricular chemotherapy may be helpful even when anaplastic oligodendrogliomas disseminates to leptomeninges.

Treatment Results of Intracranial Aneurysms by Wrapping and Coating

OBJECTIVE: Although surgical clipping of intracranial aneurysm is the definite method of treatment, there remains a small number of patients in whom surgical clipping is not technically possible. In such difficult cases, surgeon has to consider other therapeutic alternatives. In this report, we analyze our aneurysmal cases treated by wrapping and coating method and evaluate their surgical outcome and follow-up results. METHOD: Among the total of 877 patients operated from 1990 to 1999 for intracranial aneurysms at our hospital, 40 cases(4.6%) were treated by wrapping and coating method. They included 24 cases of single ruptured aneurysms and 16 with unruptured ones in multiple aneurysms. Wrapping with temporalis muscle and/or muslin gauze and coating with bioadhesive agent such as fibrin glue were performed. RESULT: Wrapping and coating method was performed mostly to the anterior communicating artery aneurysm (35%), and mostly because of the broad-based neck of an aneurysm(43%). At the time of discharge, 30 out of 40 patients(80%) showed favourable outcome and three cases died. The patients were monitored for average of 37 months(3-75 months). Among 24 cases with single ruptured aneurysm, 4 cases(17%) had early rebleeding within 6 months from the initial hemorrhage, and such rebleeding occurred within the first postoperative month in 3 cases. However, there was no rebleeding after the 6 months. Among 16 patients whose aneurysms were unruptured ones, none of them showed bleeding episode. CONCLUSION: It seems likely that the wrapping and coating method would be some help to prevent the rebleeding of an intracranial aneurysm. In order to obtain more accurate results regarding the efficacy of such method, it will be necessary to perform a multi-center study for longer follow-up periods and various wrapping and coating materials.

Craniopharyngioma: Comparison of Tumor Characteristics Relevant with Initial Symptomatology between Children and Adults

OBJECTIVES: The craniopharyngioma is a benign tumor located at least in part in the suprasellar cistern. However, the symptoms and signs from this tumor may be determined not only by the location of the tumor but also by its size and the age of the patient. The objective of our study is to analyze retrospectively the clinical manifestations of craniopharyngiomas with regards to tumor characteristics in children and adults. MATERIALS AND METHODS: Twenty-three patients(16 adults, 7 children) treated for craniopharyngioma between 1990 and 1999 were studied to demonstrate the relationship of tumor size, growth pattern, and its invasiveness with clinical symptoms. As part of the assessment, 16 adults(M:F=8:8, mean age:43.7 years) and 7 children(M:F=5:2, mean age:10.1 years) underwent magnetic resonance(MR) imaging and computerized tomography(CT) scanning with a three-dimensional volume acquisition sequence. RESULTS: The three major cardinal signs were defined to increased intracranial pressure, endocrine dysfunction, and visual problems. The tumor size in child group was larger than that in adult group. Also, visual problems, symptoms of increased intracranial pressure and hydrocephalus were more frequently observed in child group. However, endocrine dysfunction and neuropsychological symptoms related with hypothalamic connections to the thalamus, pituitary, frontal lobe, and other cortical areas were more frequent in adult group. Conclusions: In our series, the tumor size and invasiveness of craniopharyngioma revealed to be relevent with initial symptoms of increased intracranial pressure and visual symptoms which were more frequent in child group. As for the growth pattern, we did not find major difference between adults and children.

Endovascular Treatment of Incompletely Clipped Cerebral Aneurysm

Residual aneurysm is a challenging problem after clipping procedure for the aneurysms. The anthors describe one patient in whom endovascular treatment was sucessfully done to treat residual aneurysm after surgical clipping. We discussed the role of endovascular coil occlusion in case of incomplete surgical obliteration of aneurysms.

Primary Spinal Epidural Lymphoma Mimicking Epidural Abscess in a Diabetic

Primary spinal epidural lymphoma(SEL), i.e. occurring in the absence of any detectable extraspinal lymphoproli-ferative disorder, is an unusual cause of spinal cord compression. The authors report a 48-year-old, diabetic woman presented with back pain followed by acute paraparesis and voiding difficulty. She had been treated with acupunctures on her back before admission, and complete blood count showed leukocytosis with neutrophilia and increased erythrocyte sedimentation rate(ESR). Thoracic spine magnetic resonance imaging(MRI) revealed an epidural mass extending from T5 to T8 with compression of the spinal cord. Emergency decompressive laminectomy was performed with a tentative diagnosis of spinal epidural abscess, but a B-cell lymphoma was final pathologic diagnosis. Further staging showed no other sites of lymphoma, and the spinal lesion was treated by chemotherapy and radiotherapy. The authors stress that primary SEL can mimic spinal epidural abscess(SEA) in the diabetic patient and should be a diagnostic consideration in patients with a syndrome of acute spinal cord compression manifested by a prodrome of back pain and neuroimaging consistent with an epidural compressive lesion, especially in a diabetic.

Osteochondroma of the Lumbar Spines without Clear Demarcation from Surrounding Normal bone Tissues

Spinal osteochondroms are very rare, and are thought to arise through a process of progressive endochondral ossification of aberrant cartilage of a growth plate, as a consequence of congenital defect or trauma. A case of diffuse type osteochondroma involving the posterior elements of L1-L5 that progressed after laminectomy in a 33-year-old man is reported. Usually, the spinal osteochondroma shows clear demarcation between tumor margin and normal spine elements, and can be exised completely. However, there was no clear demarcation between tumor and normal spine element in our case and therefore it was not possible to removal completely.

Primary Non-Hodgkin's Lymphomas Presenting with Extradural Spinal Cord Compression as the Initial Manifestation

No abstract available.

Solitary Cysticercus Granuloma of the Brainstem: Case Report

No abstract available.

Intracranial Magnetic Resonance Angiography-Its Role in the Approach to Ischemic Stroke

No abstract available.

Difference of Neuronal Recovery by Incubation Condition after Transient Hypoxia

No abstract available.

Unilateral Hydrocephalus in Congenital Atresia of the Foramen of Monro

No abstract available.

Evaluation of Apoptosis in the Normal Rat Brain after Intraoperative Irradiation

Radiation therapy is one of the most important treatment modalities following surgery of the primary malignant or metastatic brain tumors. But radiation can be harmful to normal healthy brain tissues around the tumor. There have been numerous reports of radiation induced damage such as delayed necrosis to human brain after therapeutic exposure. Apoptosis is a form of cell death with morphological and biochemical features that differ from those of necrosis. The aim of this study is to evaluate the apoptosis in normal rat brain after irradiation. Twenty one Sprague-Dawley rats were given a single dose of 10 Gy using high dose rate Ir-192 over 5 minutes at the right frontal region. Apoptosis was evaluated by the TUNEL method(In-situ end labelling technique) and mutant p53 protein, bc1-2 and bax genes were evaluated by immunohistochemical stain. Apoptosis was assessed at 1 week(group A, n=5), 2 week(group B, n=), 4 week(group C, n=), 6 week(group D, n=), 8 week(group E, n=) after irradiation. Apoptosis was noted with 20% of cases(1/5) in group A, 40% of cases(2/5) in group B, 60% of cases(3/5) in group C, 67% of cases(2/3) in group D and 100% of cases(3/3) in group E. Overall apoptosis positive rate was 52.4%(11/21). Apoptosis was most prominently found in external granular and external pyramidal layer(82%, 9/11) and found one case in internal pyramidal layer and the other one case in corticowhite matter junction. There were no positive stainning for mutant p53 protein, bc1-2 and bax gene in all cases pertaining to the phenomenon of apoptosis. In conclusion, apoptosis was evident in the rat brain after irradiation and the incidence of apoptosis was increased with time after irradiation. But the genes related to apoptosis after irradiation were not apparent in this study. Further evaluation including biochemical and clonogenic study needs to clarify the mechanism of apoptosis in normal brain after irradiation.

Atypically Located Brainstem Schwannoma

Intracranial schwannoma constitutes 8-10% of all primary intracranial tumors. The majority of them derive from cranial nerves, especially from the vestibulocochlear nerve. Intraparenchymatous schwannoma of the cent ral nervous system, on the other hand, is very rare. We report a rare case of brainstem schwannoma with the review of literature 8.