{"id":1579,"date":"2026-01-24T08:35:20","date_gmt":"2026-01-24T08:35:20","guid":{"rendered":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/2026\/01\/24\/genetics-of-sporadic-adrenocortical-tumors\/"},"modified":"2026-01-24T08:35:20","modified_gmt":"2026-01-24T08:35:20","slug":"genetics-of-sporadic-adrenocortical-tumors","status":"publish","type":"post","link":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/2026\/01\/24\/genetics-of-sporadic-adrenocortical-tumors\/","title":{"rendered":"GENETICS OF SPORADIC ADRENOCORTICAL TUMORS"},"content":{"rendered":"
Jerome Bertherat<\/div>\n
Endocrinology, Metabolism & Cancer, Cochin Institute, INSERM U567, Paris Descartes University, Referral Center for Rare Adrenal Disorders, Cochin Hospital, Paris, France <\/div>\n
Adrenocortical tumors (ACT) can be classified as benign adrenal adenomas (ACA) and malignant adrenocortical cancers (ACC), which are typically unilateral. Primary bilateral adrenal diseases are rare and can be observed as micronodular diseases (mainly primary pigmented nodular adrenocortical disease, PPNAD) and as macronodular diseases (ACTH-independent macronodular adrenocortical hyperplasia, AIMAH). The study of familial ACT has been very important initially to progress in the genetics of sporadic tumors. Unilateral ACT are monoclonal, and CGH studies have shown that the number of large molecular alterations increases with tumor size and malignancy. Nowadays various molecular alterations have been reported in sporadic ACT, most of them associated with a given tumor type, but some more broadly distributed. <\/p>\n

ACC in children can be observed in both the Li Fraumeni Syndrome (LFS) due to TP53 (located at 17p) germ line mutations, and the Beckwith-Wiedemann Syndrome (BWS). The BWS is due to alterations of the 11 p15 chromosomal region where is located the imprinted IGF-II gene. ACT in children presents almost constantly IGF-II overexpression.lnterestingly, overexpression of IGF-II as well as allelic loss (LOH) on 11 p15 and 17p13 are present in the majority of sporadic ACC in adults, due to somatic genetic alterations. Prospective follow-up of patients operated on for localized (stage I or II) unilateral ACT have demonstrated the diagnostic value of these molecular markers. Somatic TP53 mutations are present in a third of sporadic ACC in adults, and are associated with more advanced tumors and a worse outcome. PPNAD can be due to germ line inactivating PRKAR1A (Carney complex gene 1) and PDEllA4 mutations. Somatic PRKAR1A mutations have been observed in a sub group of sporadic unilateral AA responsible for Cushing's syndrome, with clinical and pathological characteristics similar to PPNAD. Germline PDEllA4 rare missense mutations are more frequent in patients with AIMAH and unilateral ACTthan in the general population. Furthermore, somatic loss of the wild type PDEllA4 allele is observed in these ACT. Therefore, PDEllA4 might playa role in the genetic predisposition to ACT. Immunohistochemistry as well as gene profiling studies have demonstrated activation of the Wnt\/13-catenin signaling pathway in ACT. In keeping with these observations, somatic activation mutations of CTNNB 1 (β-catenin) have been observed both in ACA and ACC Gene profiling studies have shown that the pattern of gene expression clearly differs between malignant and benign ACT. In keeping with the known genetics alterations in ACTthese studies have shown dysregulation of various signaling pathways important in ACT development (i.e.IGF-II, cAMP\/PKA, Wnt\/β-catenin …. ). <\/p>\n

In conclusion, various genetics alterations have been now described in sporadic ACT. This is offering new perspectives for ACT classification and point to potential interesting therapeutic targets, especially in signaling pathways that are activated by these molecular alterations. <\/div>\n","protected":false},"excerpt":{"rendered":"

Jerome Bertherat Endocrinology, Metabolism & Cancer, Cochin Institute, INSERM U567, Paris Descartes University, Referral Center for Rare Adrenal Disorders, Cochin Hospital, Paris, France Adrenocortical tumors (ACT) can be classified as benign adrenal adenomas (ACA) and malignant adrenocortical cancers (ACC), which are typically unilateral. Primary bilateral adrenal diseases are rare and can be observed as micronodular Read More<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[52,2,11],"tags":[],"class_list":["post-1579","post","type-post","status-publish","format-standard","hentry","category-volume-9-issue-2","category-journal-articles","category-volume-9"],"_links":{"self":[{"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/posts\/1579","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/comments?post=1579"}],"version-history":[{"count":0,"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/posts\/1579\/revisions"}],"wp:attachment":[{"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/media?parent=1579"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/categories?post=1579"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/tags?post=1579"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}