Adrenocortical carcinoma causes: Difference between revisions
Jump to navigation
Jump to search
No edit summary |
No edit summary |
||
| Line 70: | Line 70: | ||
*[[Neurofibromatosis type I|Neurofibromatosis type 1]] | *[[Neurofibromatosis type I|Neurofibromatosis type 1]] | ||
*[[MEN1]] | *[[MEN1]] | ||
{| style="border: 0px; font-size: 90%; margin: 3px; width: 1000px" align="center" | {| style="border: 0px; font-size: 90%; margin: 3px; width: 1000px" align="center" | ||
| Line 226: | Line 159: | ||
* [[Omphalocele]] | * [[Omphalocele]] | ||
|} | |} | ||
==References== | ==References== | ||
Revision as of 15:58, 25 September 2017
|
Adrenocortical carcinoma Microchapters |
|
Differentiating Adrenocortical carcinoma from other Diseases |
|---|
|
Diagnosis |
|
Treatment |
|
Case Study |
|
Adrenocortical carcinoma causes On the Web |
|
American Roentgen Ray Society Images of Adrenocortical carcinoma causes |
|
Risk calculators and risk factors for Adrenocortical carcinoma causes |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [2]Ahmad Al Maradni, M.D. [3]
Overview
There are no established causes for adrenocortical carcinoma.
Causes
- There are no established causes for Adrenocortical carcinoma.
- The relatively increased incidence in childhood is mainly explained by germline TP53 mutations, which are the underlying genetic cause of ACC in >50% to 80% of children.
Genetics
The genetic dissection of ACC has revealed genomic aberrations that contribute to neoplastic transformation of adrenocortical cells:
1. Clonality
- ACCs initiate from monoclonal cell populations, suggesting that mutation events lead to clonal expansion and ultimate progression to cancer.[6]
- Flow cytometry revealed aneuploidy in ACC. aneuploidy was observed in 75% of ACC.[7]
- Assessment of aneuploidy with histopathological criteria in 7 of 9 adrenal tumors revealed a high correlation with Weiss score >3 (indicative of malignancy).[8]
- No significant difference in overall survival was observed in patients with ACC exhibiting aneuploidy vs patients with ACC exhibiting diploid neoplasms.[9]
- An initial study identified elevated expression of genes involved in cell proliferation in ACC, such as IGF2, compared with increased expression of steroidogenic genes in ACA.[10]
- Giordano et al identified unique transcriptionally activated (12q and 5q) and repressed (11q, 1p, and 17p) chromosomal regions in 33 ACCs vs 22 ACAs in a microarray study.[11]
- Giordano et al (192) determined that ACC with high histological grade exhibited overexpression of cell cycle and functional aneuploidy genes and leading to the decreased survival of patients.
3. MicroRNAs
- MicroRNAs are RNAs that are important in the regulation of gene expression.
- Numerous miRNAs have been identified in the regulation of various cellular processes such as proliferation, apoptosis, and differentiation.[13]
- Dysregulation of miRNAs, such as overexpression or deletion, plays an important role in diseases.
- Mistargeting of the miRNAs, resulting in inhibition or activation of various oncogenes, tumor suppressors, and other factors important in tumor angiogenesis.[14]
- The investigation identified 14 upregulated miRNAs and 9 downregulated miRNAs unique to ACC.[15]
- Upregulated miRNAs in ACCs included miR-184, miR-210, and miR-503.
- Downregulated miRNAs included miR-214, miR-375, and miR-511.[16]
- Levels of miR-184, miR-503, and miR-511 are able to distinguish benign from malignant adrenal tumors.[16]
- MiR-483 was found to be significantly upregulated in pediatric ACCs.
- MiR-99a and miR-100 are bioinformatically predicted to target the 3- untranslated regions of IGF1R, RPTOR, and FRAP1 and were experimentally confirmed to target several components of the IGF-1 signaling pathway.[17]
4. Gene mutations
- Targeted genetic analyses have identified somatic genetic changes in TP53, MEN1, IGF2, IGF2R, and p16.[18]
- TP53 located on 17p13 is the most commonly mutated gene in ACC, present in at least one-third of ACCs.[19]
- LOH in the gene encoding p16ink/ p14arf, CDKN2A is observed in a subset of ACCs. The tumor suppressor function of this gene has been established in multiple cancers. LOH of 11q13 has been identified in 83% of samples.[20]
- MEN1 somatic mutations are unusual in sporadic ACC.[21]
- The canonical Wnt pathway, the catenin gene, and CTNNB1 have been identified as activating point mutations in over 25% of both ACAs and ACCs in children and adults.[22]
5. Chromosomal aberrations
- Comparative genomic hybridization(CGH) can identify structural chromosomal abnormalities within ACCs.[23]
- ACCs showed complex chromosomal alterations. ACCs contained multiple chromosomal gains or losses with a mean of 10 events.
- The newest study confirmed increased alterations in ACC (44%) compared with ACAs (10%).
- In ACCs, the frequently observed chromosomal gains at 5, 7, 12, 16, 19, and 20 and losses at 13 and 22 were confirmed.
- The group identified genes within these regions with potential tumorigenic potential including fibroblast growth factor 4 (FGF4), cyclin-dependent kinase 4 (CDK4), and cyclin E1(CCNE1). The study confirmed the diagnostic utility of 6 loci (5q, 7p, 11p, 13q, 16q, and 22q) in the differentiation of ACA and ACC.
- Genomic aberration at chromosomes 5, 12, and 17 are predicted to illustrate genes that initiate or maintain neoplastic transformation. Chromosome 17, specifically at 17p13, contains the well-known tumor suppressor gene TP53.
6. Epigenetic
- DNA methylation involves the addition of a methyl group to the cytosine pyrimidine ring or adenine purine ring.[24]
- Dysregulation in this process is observed in tumor cells.
- A recent study revealed hypermethylation of promoters in ACC with correlation to poor survival and identified H19, PLAGL1, G0S2, and NDRG2 as silenced genes also provided evidence about the role of methylation in ACC tumorigenesis, particularly in the 11p15 locus containing IGF2 and H19.
Hereditary syndromes associated with adrenocortical carcinoma are:
| Differential Diagnosis | Gene mutations | Clinical picture |
|---|---|---|
| Lynch syndrome | ||
| Neurofibromatosis type 1 |
| |
| MEN1[1] |
|
|
| Carney complex | ||
| BWS[2] |
References
- ↑ B. Gatta-Cherifi, O. Chabre, A. Murat, P. Niccoli, C. Cardot-Bauters, V. Rohmer, J. Young, B. Delemer, H. Du Boullay, M. F. Verger, J. M. Kuhn, J. L. Sadoul, Ph Ruszniewski, A. Beckers, M. Monsaingeon, E. Baudin, P. Goudet & A. Tabarin (2012). "Adrenal involvement in MEN1. Analysis of 715 cases from the Groupe d'etude des Tumeurs Endocrines database". European journal of endocrinology. 166 (2): 269–279. doi:10.1530/EJE-11-0679. PMID 22084155. Unknown parameter
|month=ignored (help) - ↑ H. Segers, R. Kersseboom, M. Alders, R. Pieters, A. Wagner & M. M. van den Heuvel-Eibrink (2012). "Frequency of WT1 and 11p15 constitutional aberrations and phenotypic correlation in childhood Wilms tumour patients". European journal of cancer (Oxford, England : 1990). 48 (17): 3249–3256. doi:10.1016/j.ejca.2012.06.008. PMID 22796116. Unknown parameter
|month=ignored (help)