The clinical genetics of phaeochromocytoma and paraganglioma

Gunawardane, P. T. Kavinga; Grossman, Ashley

doi:10.1590/2359-3997000000299

Cited by 18 publications

(13 citation statements)

References 56 publications

(115 reference statements)

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“…Our results do not show the sexual difference of incidence in second primary malignancy. Several studies indicate male patients have propensity to develop tumor at difficult location [7], or harbor succinate dehydrogenase subunit B (SDHB) [12] or SDH subunit D (SDHD) [15] mutational penetrance. In our study, we do find that all 4 SDHB-mutated PCC/ PGLs were all male, which is associated with an aggressive course.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Factors of Malignant Pheochromocytoma and Paraganglioma: A Combined SEER and TCGA Databases Review

Khurana

Al-Juhaishi

et al. 2019

Horm Metab Res

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Pheochromocytoma (PCC) and paraganglioma (PGL) are rare malignancies while pathogenesis is strongly influenced by genetics. The prognostic factors of these patients remain poorly defined. We aim to study the epidemiology and survival pattern by analyzing the combination of SEER and Cancer Genome Atlas (TCGA) database. Primary outcome was overall survival (OS) and disease specific survival (DSS). Between 1973 and 2013, a total of 1014 patients with PGL or PCC were analyzed. Younger age and female were associated with better outcomes. The incidence of second primary malignancy in PGL/PCC patients was about 14.6%. This population had a significant longer DSS. Other factors, including surgical resection and origin from of aortic/carotid bodies, conferred remarkable survival advantage. In contrast, distant spread portended worse prognosis. Laterality, race, positive serum catecholamine marker did not demonstrate a significant association with OS and DSS. By analyzing TCGA database with total 184 patients were identified. Eighty out of 184 patients (43.5%) had at least one pathogenic mutation. Female had higher ratio of pathogenic mutations than male (58.7% vs. 41.3%) and NF1 mutation was associated with elderly population. SHDB mutation had higher percentage in male. Twenty-nine patients (15.8%) had 2 or more primary. ATRX was the most common oncogenic mutations in metastatic cohort. In conclusion, younger age, female sex, origin from aortic/carotid bodies, complete surgical resection, regional disease, as well as concomitant second primary malignancies were associated with better prognosis. The prognostic value of radiotherapy and oncogenomics warrants further investigation.

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Section: Discussionmentioning

confidence: 99%

Prognostic Factors of Malignant Pheochromocytoma and Paraganglioma: A Combined SEER and TCGA Databases Review

Khurana

Al-Juhaishi

et al. 2019

Horm Metab Res

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“…This condition causes epigenetic changes in HIF target genes, which affects many processes including proliferation, angiogenesis, migration, apoptosis, and invasion. These events may all contribute to PPGL formation [ 19 , 35 , 38 , 41 , 42 , 43 , 44 ].…”

Section: Resultsmentioning

confidence: 99%

“…In contrast, TMEM127 mutations trigger the mTOR pathways. Another mechanism includes deactivation of the MAX suppressor gene, causing an abnormally elevated expression of cofactor MYC (proto-oncogene), resulting in the formation of PPGLs [ 14 , 38 , 39 , 40 , 41 , 43 , 44 ].…”

Section: Resultsmentioning

confidence: 99%

“…Tumors are more likely to develop in children if the father is affected or a mutation carrier himself. If the mutation is inherited from the mother, it is inactivated but still genetically transmitted [ 8 , 12 , 15 , 35 , 41 , 47 , 49 ].…”

Section: Resultsmentioning

confidence: 99%

“…The SDHB gene mutation increases the risk of renal cell carcinoma, gastrointestinal stromal tumor (GIST), and breast and papillary thyroid carcinoma, and while patients with metastatic disease should be routinely tested for the presence of the predisposing SDHB mutation, there are no guidelines regarding the screening of asymptomatic SDHx gene mutation carriers. Experts do suggest annual biochemical screening for PCC/PGLs from between the ages of five and 10, as well as full-body MRI screening for all associated tumor types every 2–5 years [ 8 , 12 , 14 , 35 , 41 , 47 , 49 ].…”

Section: Resultsmentioning

confidence: 99%

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Head and Neck Paragangliomas—A Genetic Overview

Majewska

Budny

Ziemnicka

et al. 2020

IJMS

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Pheochromocytomas (PCC) and paragangliomas (PGL) are rare neuroendocrine tumors. Head and neck paragangliomas (HNPGL) can be categorized into carotid body tumors, which are the most common, as well as jugular, tympanic, and vagal paraganglioma. A review of the current literature was conducted to consolidate knowledge concerning PGL mutations, familial occurrence, and the practical application of this information. Available scientific databases were searched using the keywords head and neck paraganglioma and genetics, and 274 articles in PubMed and 1183 in ScienceDirect were found. From these articles, those concerning genetic changes in HNPGLs were selected. The aim of this review is to describe the known genetic changes and their practical applications. We found that the etiology of the tumors in question is based on genetic changes in the form of either germinal or somatic mutations. 40% of PCC and PGL have a predisposing germline mutation (including VHL, SDHB, SDHD, RET, NF1, THEM127, MAX, SDHC, SDHA, SDHAF2, HIF2A, HRAS, KIF1B, PHD2, and FH). Approximately 25–30% of cases are due to somatic mutations, such as RET, VHL, NF1, MAX, and HIF2A. The tumors were divided into three main clusters by the Cancer Genome Atlas (TCGA); namely, the pseudohypoxia group, the Wnt signaling group, and the kinase signaling group. The review also discusses genetic syndromes, epigenetic changes, and new testing technologies such as next-generation sequencing (NGS).

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The recurrent p.(Pro540Ser) MEN1 genetic variant should be considered nonpathogenic: A case report

Villabona

Oriola

Serrano

et al. 2021

American J of Med Genetics Pt A

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Pheochromocytoma/paraganglioma (Pheo/PGL) associated with pituitary adenoma (PA) is rare in clinical practice, and a common pathogenic mechanism has been suggested owing to the germline pathogenic variants found in some cases. Our aim is to propose a reassignment for a recurrent MEN1 genetic variant found in a 54-year-old male patient with bilateral pheochromocytoma and GH-secreting PA. Pheo/PGL genes study was carried out in DNA samples from Pheo as well as PA and no pathological variants or large deletions were detected. Additionally, a MEN1 gene analysis was performed, and a heterozygous germline variant in exon 10: c.1618C>T; p.(Pro540Ser) was found. No MEN1 gene deletions/duplications were detected. In evaluating a causal relationship between the c.1618C>T MEN1 variant and both tumors, we took into account that missense variants are common pathogenic variants in MEN1, and the population frequency of this variant is too high to be considered pathogenic. His son (aged 38 and carrier) is asymptomatic, and computational analysis showed discrepancies. We propose that this recurrent variant, previously considered as likely pathogenic, subsequently as variant of uncertain significance, and likely benign should now be reclassified as benign.

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The clinical genetics of phaeochromocytoma and paraganglioma

Cited by 18 publications

References 56 publications

Prognostic Factors of Malignant Pheochromocytoma and Paraganglioma: A Combined SEER and TCGA Databases Review

Prognostic Factors of Malignant Pheochromocytoma and Paraganglioma: A Combined SEER and TCGA Databases Review

Head and Neck Paragangliomas—A Genetic Overview

The recurrent p.(Pro540Ser) MEN1 genetic variant should be considered nonpathogenic: A case report

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