| Objective:To find out the prevalence of SDHB,SDHC and SDHD mutations in patients with paraganglioma from china and to find out whether there is any difference with respect to the data published in other populations. The study is designed to provide the basis for further study of molecular diagnosis and molecular genetics of paraganglioma and faciliate early detection and early treatment for paragangliomas.Methods:Twenty four sporadic PGLs with complete clinical and pathological data were investigated. All of them were preliminarily diagnosed at Tianjin Medical University cancer hospital from 2006 April to 2011 January. We also have 34 normal blood samples investigated. Peripheral venous bloods were gained and genomic DNA was extracted by TKM method, and organization genomic DNA was extracted by Blood/cell/organization genomic DNA extracted kit. Each amplification fragment of SDHB,SDHC and SDHD exons gained through PCR are sequenced directly after purification. Finaly the results of sequencing are compaired with standard sequence published in the NCBI net using the software of BLAST.Results:1. Two sporadic cases studied carried a germline mutation in SDHD-exon 2 which located in the 112th base pair, C is substituted by T, making the 38th codon change from CGA to TGA(R38X). One patient is female.has an onset age for 29, pathological type is benign leision. Another patient is male, has an onset age for 27, pathological type is malignant tendency leision.2. One sporadic cases studied carried a germline mutation in SDHD-exon 3 which located in the 311th base pair, A is substituted by C, making the 104th codon change from CAC to CCC(H104P). The patient has a onset age for 22, pathological type is benign leision, performance is voice hoarse.Pathological type is benign leision, left submaxill vein with tumor embolism.3. Two sporadic cases studied carried a germline mutation in SDHB-exon 1 which located in the 18th base pair, C is substituted by A, making the 6th codon change from GCC to GCA (A6A). One patient is male,has an onset age for 17, pathological type is malignant leision, infringed neural. Another patient is female, has an onset age for 30, pathological type is malignant leision, infringed neural.4. One sporadic cases studied carried a germline mutation in SDHB-exon 6 which located in the 594th base pair, C is substituted by A, making the 18th codon change from AGC to AGA (S198R). The patient has a onset age for 58, performance is voice hoarse.Pathological type is benign leision,encroached tunic.5. In this study SDHC mutations were not found in sporadic patients with single paraganglioma from china.Conclusions:1. In this study 25.0% sporadic paraganglioma patients carried a mutation in SDH: three mutation in SDHB and three mutation in SDHD. In this study SDHC mutations were not found in sporadic patients with single paraganglioma from china. SDHC gene prevalence is low in this group of patients.2. In this study,4/21(19. 1%)benign patients have SDH mutation. One is SDHB gene mutation, three is SDHD gene mutation. It is consistent with the view that SDHD gene mutations mainly related with the benign paragangliomas. One missense germline mutation in SDHB-exon 6, S198R. Two same-sense germline mutation in SDHD-exon 2, R38X; a missense germline mutation in SDHD-exon 3, H104P. H104P may be a new mutation type.3. In this study,2/3(66.7%)mlignant patients have SDH gene mutation. Both carried samesense mutation in SDHB-exon 1 A6A, which may suggest that A6A may affect the phenotype of paraganglioma. It is consistent with the view that SDHB gene mutations mainly related with the malignant paragangliomas.4. In this study,3/4 benign paraganglioma patients that carried with SDH gene mutations performance invasive behaviour, it is prompt that SDH gene mutation maybe related with biological behavior.5. SDH test is of significance to early onset, pathologically malignant and aggressive behavior Chinese patients with para-ganglioma.. |
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