Absent Ras Gene Mutations in Human Adrenal Cortical Neoplasms and Pheochromocytomas

Moul, Judd W.; Bishoff, Jay T.; Theune, Sheila M.; Chang, Esther H.

doi:10.1016/s0022-5347(17)36397-8

Cited by 41 publications

(22 citation statements)

References 32 publications

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“…The three ras proteins (H, N, and K) are one of the most commonly mutated oncogenes in human cancers (Shields et al 2000). Controversial data are present in the literature: Lin et al (1998) found K-ras mutations in about 50% of tumor tissues of Conn's adenomas and no mutations are observed in H-ras, while Moul et al (1993) and Ocker et al (2000) did not identify Ras mutations. Figure 3 The Wnt signaling pathway.…”

Section: Ras Oncogenementioning

confidence: 99%

Adrenocortical cancer: pathophysiology and clinical management

Libé¹,

Fratticci²,

Bertherat³

2007

Endocr Relat Cancer

237

159

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Adrenocortical cancer (ACC) is a rare tumor with a poor prognosis. By contrast, benign adrenocortical tumors are frequent, underlying the importance of a correct diagnosis of malignancy of such tumors. ACC can be diagnosed by the investigation of endocrine signs of steroid excess, symptoms due to tumor growth or an adrenal incidentaloma. Hormonal investigations demonstrate in most ACC steroid oversecretion, the dominant characteristics being a co-secretion of cortisol and androgens. Imaging by CT-scan or MRI shows a large heterogeneous tumor with a low fat content. Careful pathological investigation with the assessment of the Weiss score is important for the diagnosis of malignancy. Molecular markers can also be helpful and in the future might be important for prognosis. Tumors localized to the adrenal gland (McFarlane stages 1 and 2) have a better outcome than invasive and metastatic tumors (stages 3 and 4). Tumor removal by a specialized team is crucial for treatment and should always aim at complete removal. In patients with metastatic or progressive disease, medical treatment is started with mitotane that requires a close monitoring of its blood level. Surgery is indicated when possible for local recurrence but also in some cases of metastasis. Local treatment (radiofrequency, chemoembolization, and radiation therapy) can have some indications for metastatic disease. In patients with disease progression cytotoxic chemotherapy can be used. Despite the best care, the overall prognosis of ACC is poor with a 5-year survival rate below 30% in most series. Therefore, progress in the understanding of the pathophysiology of ACC is important. Despite the rarity of ACC, significant advances have been made in the understanding of its pathogenesis the last decade. These progresses came mainly from the study of the genetics of ACC, both at the germline level in rare familial diseases, and at the somatic level by the study of molecular alterations in sporadic tumors. These advances underline the importance of genetic alterations in ACC development and point-out to various chromosomal regions (2, 11p15, 11q, 17p13) and genes (IGF-II, p53, b-catenin, ACTH receptor). This review will summarize these advances as well as the current clinical management of ACC.

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Section: Ras Oncogenementioning

confidence: 99%

Adrenocortical cancer: pathophysiology and clinical management

Libé¹,

Fratticci²,

Bertherat³

2007

Endocr Relat Cancer

237

159

View full text Add to dashboard Cite

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“…Activating N-Ras mutations were identified in 12.5% of ACCs and ACAs tested whereas no mutations were found in K-and H-Ras (Yashiro et al, 1994). In a smaller number of tumors, Moul et al (1993) did not detect any point mutations in N-, H-or K-Ras. Finally, Ocker et al (2000) also did not identify K-Ras mutations in 40 AAs.…”

Section: Specific Genetic Alterations In Sporadic Adrenocortical Tumorsmentioning

confidence: 73%

Insights into the role of genetic alterations in adrenocortical tumorigenesis

Herbet

Feige

Thomas

2009

Molecular and Cellular Endocrinology

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Whereas benign adrenocortical tumors are frequent in the population, adrenocortical carcinoma (ACC) is a rare cancer. Significant advances in the understanding of the pathogenesis of sporadic ACCs have been possible through the study of hereditary syndromes responsible for ACCs. The genetic alterations involved in these syndromes have also been found in sporadic ACCs. Several specific genes have been shown to be altered in sporadic ACCs. Despite these progresses, the underlying sequence(s) of events remains( ) to be elucidated. Progressive transformation of a normal tissue into a benign tumor and ultimately into a carcinoma occurs via accumulation of genetic and epigenetic alterations. Likewise, a multistage model has been proposed for the adrenal tumor development. This review summarizes the molecular alterations likely involved in the multistage tumorigenesis and describes a mouse model which allows us to evaluate the effect of individual genes or combination of genes in the development of adrenocortical tumors.

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“…60 However, these findings were not corroborated in two other cohorts of adrenocortical tumours. 61,62 No significant MEN1 gene mutations were apparent in sporadic ACT, although LOH of the 11q13 band harbouring menin gene was frequent in ACC. 63 More recently, steroidogenic factor 1 (SF1) gene, a master regulator of adrenal development and steroidogenesis, was seen to be overexpressed in many childhood and adult ACT.…”

Section: Tp53mentioning

confidence: 99%

Genetic aspects of adrenocortical tumours and hyperplasias

Mazzuco

Durand

Chapman

et al. 2012

Clinical Endocrinology

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SummaryAdrenocortical tumours (ACT), which include adenomas, carcinomas and adrenal hyperplasia, may be associated with genetic syndromes, such as Li–Fraumeni syndrome, Beckwith–Wiedemann syndrome, multiple endocrine neoplasia type 1, familial adenomatous polyposis and Carney complex. Genetic defects have been found to be responsible for the disease in most of these syndromes, allowing genetic counselling to affected patients and family members. Here, we summarize the clinical criteria of these hereditary syndromes and briefly describe the genetic alterations related to them. In addition, we discuss the involvement of various genetic defects in the development of sporadic adrenocortical tumours.

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Absent Ras Gene Mutations in Human Adrenal Cortical Neoplasms and Pheochromocytomas

Cited by 41 publications

References 32 publications

Adrenocortical cancer: pathophysiology and clinical management

Adrenocortical cancer: pathophysiology and clinical management

Insights into the role of genetic alterations in adrenocortical tumorigenesis

Genetic aspects of adrenocortical tumours and hyperplasias

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