Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 44-year-old woman complained of headache and palpitation. Magnetic resonance imaging showed bilateral adrenal tumors 10 x 9 cm in size on the left side and 8 x 4 cm in size on the right side. CT scan revealed a 0.7 x 0.7 cm mass in the thyroid. Hormonal examinations showed high values of urinary cathecholamines and serum calcitonin. DNA sequence analysis of peripheral white blood cells revealed that codon 634 in exon 11 of the RET gene was mutated from TGC (Cys) to TAC (Tyr). From these findings, a diagnosis was made of MEN2A with bilateral adrenal pheochromocytomas and medullary thyroid carcinoma. Bilateral adrenalectomy and thyroidectomy were performed. The same mutation of the RET gene was detected in all her 3 children, in two of whom, early stage medullary thyroid carcinoma was detected and thyroidectomy was performed. DNA analysis of the RET gene was useful for the diagnosis of carriers of MEN2A and the early detection of medullary thyroid carcinoma.
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PMID:[A case of multiple endocrine neoplasia type 2A (MEN2A) with a mutation in the RET gene]. 1044 82

Pheochromocytomas and paragangliomas are tumors arising from chromaffin cells. These tumors produce catecholamines and are typically found with symptoms and signs that may include hypertension (persistent or episodic), palpitations, headache and sweating. So far, 10 different genes have been associated with both tumors and other genes are expected to be detected. Pheochromocytoma and paraganglioma can occur as a part of genetic syndromes - familial paragangliomas (SDH genes, SDHAF2 gene), von Hippel-Lindau syndrome (VHL gene), multiple endocrine neoplasia type 2 (RET gene), and neurofibromatosis type 1 (NF1 gene). These tumors may be the first and only manifestation of these genetic syndromes. Patients with SDHB mutations are at high risk to develop malignant disease and unfortunately current therapeutic options for malignant form of disease are poor. Genetic testing plays a key role in the management of these tumors and therefore not only index patients with pheochromocytoma but also relatives should be tested. Management of this disease requires multidisciplinary cooperation and should be performed in the specialized medical centres.
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PMID:[Hereditary pheochromocytoma and paraganglioma]. 2292 Feb 2

The U.S. Food and Drug Administration (FDA) approved vandetanib in April 2011 for the treatment of unresectable, locally advanced or metastatic medullary thyroid cancer (MTC). In Europe it was approved in March 2012, but only for the treatment of aggressive and symptomatic MTC. This small molecule is a tyrosine kinase inhibitor of several growth factors involved in cellular proliferation and angiogenesis, including the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor receptors 2 and 3 (VEGFR-2, VEGFR-3). In addition, vandetanib is an inhibitor of the RET (rearranged during transfection) gene, a proto-oncogene often mutated in familial MTC. Since MTC is a rare disease, for which no previous medical therapies are approved, vandetanib is the first drug shown to be effective in a large phase III trial treating patients with metastatic or locally advanced MTC. Common adverse events are diarrhea, nausea, hypertension, headache and QT prolongation that are manageable and are commonly outweighed by the benefits of vandetanib in terms of delaying disease progression and inducing tumor response.
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PMID:Vandetanib therapy in medullary thyroid cancer. 2317 Mar 8

Olfactory neuroblastoma (ONB) is a rare cancer originating in the olfactory epithelium of the nasal vault. The recurrence rate of ONB is high, as the standard treatment of surgery followed by radiotherapy and/or chemotherapy is usually unsuccessful. The use of targeted therapy based on individual genomic variations after cancer relapse has not been reported. Here, we present the case of a 44-year-old man who was diagnosed with recurrent ONB and treated with a regimen developed using whole exome sequencing. Potential targets were first identified and then matched to appropriate drugs. Gene mutations in the genes encoding EGFR, FGFR2, KDR, and RET were discovered in the patient's tumor tissue by whole exome sequencing and the patient was treated with a combination of the targeted drugs cetuximab and sunitinib. Five days after treatment, enhancement magnetic resonance imaging showed a 65% reduction in tumor size, and the Visual analog scale headache scores went down to 2/10 from 10/10. Repeat imaging at 1 month showed a complete response.This study represents the first demonstration of an effective personalized treatment of ONB by targeted drugs, and sheds light on how precision medicine can be used to treat recurrent ONB that fails to respond to routine tumor resection, radiotherapy, and/or chemotherapy.
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PMID:Recurrent Olfactory Neuroblastoma Treated With Cetuximab and Sunitinib: A Case Report. 2714 58

Introduction: Pheochromocytomas (PCCs), paragangliomas (PGLs), ganglioneuroblastomas (GNBs), and ganglioneuromas (GNs) are neuroendocrine neoplasms (NENs) that were thought to share a common embryologic origin from neural crest cells. However, they rarely occur concurrently and recurrently. We describe the case of a 40-years-old woman with "composite PCC-GN" and multiple NENs and neuroblastic tumors. Case presentation: The patient was first referred to our department at the age of 15 years for paroxysmal hypertension, headache, sweating, and watery diarrhea. Her personal history included the diagnosis of a pelvic GNB with lumbar-aortic lymph node metastases at 11 months. Her family history was positive for cerebral glioblastoma multiforme (father). An abdominal ultrasound showed a right adrenal mass that histologically was a "composite adrenal PCC-GN." The symptoms disappeared after surgery. At the age of 20 years, the symptoms returned: computed tomography (CT) and 131I-metaiodobenzylguanidine (MIBG) scintigraphy showed an inter-aortocaval mass, found histologically to be an inter-aortocaval PGL. Her symptoms reappeared again at 28 years: CT and magnetic resonance imaging revealed four left adrenal gland nodules, found histologically to be multifocal PCCs with some atypia. Genetic screening for VHL, RET, NF1, Tp53, SDHD, SDHB, SDHC, SDHAF2, SDHAF3, SDHA, and TMEM127 was negative. Mutational analysis of the MAX gene revealed the presence of a novel heterozygous variant, c299G>C (p.Arg100Pro, NM_002382.5) that the bioinformatics prediction programs defined as noxious and causative of pathology. Conclusion: This report represents the first description of a co-occurrence of multiple composite PCC-GN and neuroblastic tumors. The long timeline of the presentation of the NENs/neuroblastic tumors from infancy to adulthood requires a lifelong follow-up for this patient. Moreover, the importance of this case lies in the presence of a novel MAX gene variant deleterious, harmful, and causative of pathology, confirmed by Sanger sequencing and never been associated before with multiple composite PCC-GN. The present case underlines the importance of precision medicine and molecular diagnoses for hereditary pheochromocytomas and paragangliomas, suggesting that when they occur in early childhood, it is necessary to perform an extensive genetic investigation and a lifelong follow-up.
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PMID:A Novel MAX Gene Mutation Variant in a Patient With Multiple and "Composite" Neuroendocrine-Neuroblastic Tumors. 3250 44