Adrenocortical carcinoma causes: Difference between revisions

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Latest revision as of 15:23, 17 October 2017

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] Mohammed Abdelwahed M.D [4]

Overview

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 more than 50% to 80% of children.

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

Hereditary syndromes associated with adrenocortical carcinoma are:

Lynch syndrome


Associated conditions	Gene mutations	Clinical picture
Lynch syndrome^[1]	MSH2, MSH6, MLH1, PMS2	Colorectal cancer Endometrial cancer Sebaceous neoplasms Ovarian cancer Pancreatic cancer Brain cancer
Neurofibromatosis type 1	NF1	Malignant peripheral nerve sheet tumor Pheochromocytoma Café au lait spots Neurofibroma Optic glioma Lisch nodule Skeletal abnormalities
MEN1^[2]	MENIN	Foregut neuroendocrine tumors Pituitary tumors Parathyroid hyperplasia Collagenoma Angiofibroma Adrenal adenoma/hyperplasia
Carney complex	PRKAR1A	Adrenal disease Sertoli cell tumors Thyroid adenoma Myxoma Somatotroph pituitary adenoma
BWS^[3]	IGF2, CDKN1C, H19	Wilm’s tumor Hepatoblastoma Macrosomia Adrenocortical cytomegaly Adrenal adenoma Adrenal cyst Hemihypertrophy Macroglossia Omphalocele

References

↑ Carethers JM, Stoffel EM (2015). "Lynch syndrome and Lynch syndrome mimics: The growing complex landscape of hereditary colon cancer". World J Gastroenterol. 21 (31): 9253–61. doi:10.3748/wjg.v21.i31.9253. PMC 4541378. PMID 26309352.
↑ 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)

Template:WikiDoc Sources

[pmid26309352-1] Carethers JM, Stoffel EM (2015). "Lynch syndrome and Lynch syndrome mimics: The growing complex landscape of hereditary colon cancer". World J Gastroenterol. 21 (31): 9253–61. doi:10.3748/wjg.v21.i31.9253. PMC 4541378. PMID 26309352.

[2] 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)

[3] 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)

[1]

[2]

[3]

@@ Line 1: / Line 1: @@
 __NOTOC__
 {{Adrenocortical carcinoma}}
-{{CMG}} {{AE}} {{RT}}{{AAM}}
+{{CMG}}; {{AE}} {{RT}} {{AAM}} {{MAD}}
 ==Overview==
-There are no established causes for adrenocortical carcinoma.
+There are no established causes for adrenocortical carcinoma. The relatively increased [[incidence]] in childhood is mainly explained by [[germline]] [[TP53 (gene)|TP53]] [[mutations]], which are the underlying [[Genetics|genetic]] cause of ACC in more than 50% to 80% of children.
 ==Causes==
-*There are no established causes for Adrenocortical carcinoma
+*There are no established causes for adrenocortical carcinoma.
+*The relatively increased [[incidence]] in childhood is mainly explained by [[germline]] [[TP53 (gene)|TP53]] [[mutations]], which are the underlying [[Genetics|genetic]] cause of ACC in >50% to 80% of children.
 == Genetics ==
-The genetic dissection of ACC has revealed [[Genomics|genomic]] aberrations that contribute to neoplastic transformation of adrenocortical cells:
+=== Hereditary syndromes  associated with adrenocortical carcinoma are: ===
+* [[Lynch syndrome]]
-'''''1. [[Clone (cell biology)|Clonality]]'''''
+*[[Beckwith-Wiedemann syndrome]]
-* ACCs initiate from [[Monoclonal|monoclonal cell]] populations, suggesting that [[mutation]] events lead to [[Clonal selection|clonal expansion]] and ultimate progression to [[cancer]].<sup>[[Adrenocortical carcinoma pathophysiology#cite note-pmid7915195-6|[6]]]</sup>
+*[[Carney complex]]
-* [[Flow cytometry]] revealed [[aneuploidy]] in ACC. [[aneuploidy]] was observed in 75% of ACC.<sup>[[Adrenocortical carcinoma pathophysiology#cite note-pmid7910530-7|[7]]]</sup>
+*[[Neurofibromatosis type I|Neurofibromatosis type 1]]
-* Assessment of [[aneuploidy]] with [[histopathological]] criteria in 7 of 9 [[Adrenal tumor|adrenal tumors]] revealed a high correlation with Weiss score >3 (indicative of [[malignancy]]).<sup>[[Adrenocortical carcinoma pathophysiology#cite note-pmid3617290-8|[8]]]</sup>
+*[[MEN1]]
-* No significant difference in overall survival was observed in patients with ACC exhibiting [[aneuploidy]] vs patients with ACC exhibiting [[Diploids|diploid]] [[Neoplasm|neoplasms]].<sup>[[Adrenocortical carcinoma pathophysiology#cite note-pmid2403197-9|[9]]]</sup>
+{| style="border: 0px; font-size: 90%; margin: 3px; width: 1000px" align="center"
-'''''2. [[Gene expression]] [[DNA microarray|arrays]]'''''
-* An initial study identified elevated [[Gene expression|expression of genes]] involved in cell proliferation in ACC, such as ''[[IGF2]]'', compared with increased [[Gene expression|expression]] of steroidogenic [[genes]] in ACA.<sup>[[Adrenocortical carcinoma pathophysiology#cite note-pmid15613424-10|[10]]]</sup>
-* Giordano et al identified unique [[Transcription (genetics)|transcriptionally]] activated (12q and 5q) and repressed (11q, 1p, and 17p) [[chromosomal]] regions in 33 ACCs vs 22 ACAs in a [[DNA microarray|microarray]] study.<sup>[[Adrenocortical carcinoma pathophysiology#cite note-pmid19147773-11|[11]]]</sup>
+|+
+! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Associated conditions}}
+! style="background: #4479BA; width: 300px;" | {{fontcolor|#FFF|Gene mutations}}
+! style="background: #4479BA; width: 300px;" | {{fontcolor|#FFF|Clinical picture}}
+|-
+| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |[[Lynch syndrome]]<ref name="pmid26309352">{{cite journal| author=Carethers JM, Stoffel EM| title=Lynch syndrome and Lynch syndrome mimics: The growing complex landscape of hereditary colon cancer. | journal=World J Gastroenterol | year= 2015 | volume= 21 | issue= 31 | pages= 9253-61 | pmid=26309352 | doi=10.3748/wjg.v21.i31.9253 | pmc=4541378 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26309352  }}</ref>
+| style="padding: 5px 5px; background: #F5F5F5;" |
+* [[MSH2]], [[MSH6]], [[MLH1]], [[PMS2]]
+|
+* [[Colorectal cancer]]
+* [[Endometrial cancer]]
+* [[Sebaceous gland carcinoma|Sebaceous neoplasms]]
+* [[Ovarian cancer]]
+* [[Pancreatic cancer]]
+* [[Brain cancer]]
+|-
+| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |[[Neurofibromatosis type I|Neurofibromatosis type 1]]
+|
+* [[NF1]]
+|
+* [[Malignant]] [[Peripheral nervous system|peripheral nerve]] [[Nerve sheath|sheet]] [[tumor]]
+* [[Pheochromocytoma]]
+* [[Café au lait spot|Café au lait spots]]
+* [[Neurofibroma]]
+* [[Optic nerve glioma|Optic glioma]]
+* [[Lisch nodule]]
+* Skeletal abnormalities
+|-
+| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |[[Multiple endocrine neoplasia type 1|MEN1]]<ref>{{Cite journal
-* Giordano et al (192) determined that ACC with high [[histological]] [[Grading (tumors)|grade]] exhibited overexpression of [[cell cycle]] and functional [[aneuploidy]] [[genes]] and leading to the decreased survival of patients.
+ | author = [[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]]
+ | title = Adrenal involvement in MEN1. Analysis of 715 cases from the Groupe d'etude des Tumeurs Endocrines database
+ | journal = [[European journal of endocrinology]]
+ | volume = 166
+ | issue = 2
+ | pages = 269–279
+ | year = 2012
+ | month = February
+ | doi = 10.1530/EJE-11-0679
+ | pmid = 22084155
+}}</ref>
+|
+* MENIN
+|
+* [[Foregut]] [[neuroendocrine tumors]]
+* [[Pituitary tumors]]
+* [[Parathyroid gland|Parathyroid]] [[hyperplasia]]
+* Collagenoma
+* [[Angiofibroma]]
+* [[Adrenal adenoma]]/[[hyperplasia]]
+|-
+| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |[[Carney complex]]
+|
+* [[PRKAR1A]]
+|
+* [[Adrenal disease]]
+* [[Sertoli cell]] [[tumors]]
+* [[Thyroid adenoma]]
+* [[Myxoma]]
+* [[Somatotrope|Somatotroph]] [[pituitary adenoma]]
+|-
+| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |[[BWS]]<ref>{{Cite journal
-* Expression levels of ''BUB1B,'' ''[[PINK1]], and [[DLG7]]'' ''are'' identified in ACC.<sup>[[Adrenocortical carcinoma pathophysiology#cite note-pmid19139432-12|[12]]]</sup>
+ | author = [[H. Segers]], [[R. Kersseboom]], [[M. Alders]], [[R. Pieters]], [[A. Wagner]] & [[M. M. van den Heuvel-Eibrink]]
+ | title = Frequency of WT1 and 11p15 constitutional aberrations and phenotypic correlation in childhood Wilms tumour patients
-==== 3. '''''[[MicroRNAs]]''''' ====
+ | journal = [[European journal of cancer (Oxford, England : 1990)]]
-* [[MicroRNAs]] are [[RNA|RNAs]] that are important in the regulation of [[gene expression]].
+ | volume = 48
-* Numerous [[MicroRNA|miRNAs]] have been identified in the regulation of various [[cellular]] processes such as [[proliferation]], [[Apoptosis|apoptosis,]] and [[differentiation]].<sup>[[Adrenocortical carcinoma pathophysiology#cite note-pmid21116305-13|[13]]]</sup>
+ | issue = 17
-* Dysregulation of miRNAs, such as overexpression or deletion, plays an important role in diseases.
+ | pages = 3249–3256
-* Mistargeting of the miRNAs, resulting in inhibition or activation of various [[oncogenes]], [[Tumor suppressor|tumor suppressors]], and other factors important in [[tumor]] [[Angiogenesis|angiogenesis.]]<sup>[[Adrenocortical carcinoma pathophysiology#cite note-pmid22337054-14|[14]]]</sup>
+ | year = 2012
-* The investigation identified 14 upregulated miRNAs and 9 downregulated miRNAs unique to ACC.<sup>[[Adrenocortical carcinoma pathophysiology#cite note-pmid19996210-15|[15]]]</sup>
+ | month = November
-* Upregulated miRNAs in ACCs included miR-184, miR-210, and miR-503.
+ | doi = 10.1016/j.ejca.2012.06.008
-* Downregulated miRNAs included miR-214, miR-375, and miR-511.<sup>[[Adrenocortical carcinoma pathophysiology#cite note-pmid19546168-16|[16]]]</sup>
+ | pmid = 22796116
-* Levels of miR-184, miR-503, and miR-511 are able to distinguish benign from [[malignant]] [[Adrenal tumor|adrenal tumors]].<sup>[[Adrenocortical carcinoma pathophysiology#cite note-pmid19546168-16|[16]]]</sup>
+}}</ref>
-* 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.<sup>[[Adrenocortical carcinoma pathophysiology#cite note-pmid20484036-17|[17]]]</sup>
+* [[IGF2]], [[CDKN1C]], [[H19 (gene)|H19]]
+|
-==== 4. '''''[[Gene mutation|Gene mutations]]''''' ====
+* [[Wilm's tumor|Wilm’s tumor]]
-* Targeted [[Genetics|genetic]] analyses have identified somatic [[Genetics|genetic]] changes in ''[[TP53 (gene)|TP53]]'', ''[[MEN1]]'', [[Insulin-like growth factor 2|''IGF2'',]] ''[[IGF2R]]'', and ''[[P16 (gene)|p16]]''.<sup>[[Adrenocortical carcinoma pathophysiology#cite note-pmid11454518-18|[18]]]</sup>
+* [[Hepatoblastoma]]
+* [[Macrosomia]]
-* ''[[TP53 (gene)|TP53]]'' located on 17p13 is the most commonly mutated [[gene]] in ACC, present in at least one-third of ACCs.<sup>[[Adrenocortical carcinoma pathophysiology#cite note-pmid22504887-19|[19]]]</sup>
+* [[Adrenocortical]] cytomegaly
-* LOH in the gene encoding [[P16INK4a|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.<sup>[[Adrenocortical carcinoma pathophysiology#cite note-pmid10022445-20|[20]]]</sup>
+* [[Adrenal adenoma]]
-* ''[[MEN1]]'' somatic mutations are unusual in sporadic ACC.<sup>[[Adrenocortical carcinoma pathophysiology#cite note-pmid17854394-21|[21]]]</sup>
+* [[Adrenal Gland|Adrenal]] [[cyst]]
-* The canonical [[Wnt signaling pathway|Wnt pathway]], the [[Catenin|catenin gene]], and ''CTNNB1'' have been identified as activating point mutations in over 25% of both ACAs and ACCs in children and adults.<sup>[[Adrenocortical carcinoma pathophysiology#cite note-pmid18647815-22|[22]]]</sup>
+* [[Hemihypertrophy]]
+* [[Macroglossia]]
-==== 5. '''''[[Chromosomal aberration|Chromosomal aberrations]]''''' ====
+* [[Omphalocele]]
-* [[Comparative genomic hybridization]]([[Comparative genomic hybridization|CGH]]) can identify structural [[chromosomal]] abnormalities within ACCs.<sup>[[Adrenocortical carcinoma pathophysiology#cite note-pmid23093492-23|[23]]]</sup>
+|}
-* 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|fibroblast growth factor 4]] (''[[FGF4]]''), [[cyclin-dependent kinase 4]] (''[[CDK4]]''), and [[cyclin E1]]([[CCNE1|''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 [[Neoplasm|neoplastic]] transformation. [[Chromosome]] 17, specifically at 17p13, contains the well-known [[tumor suppressor gene]] ''[[TP53 (gene)|TP53]]''.
-=== 6. '''''[[Epigenetics|Epigenetic]]''''' ===
-* [[DNA methylation]] involves the addition of a [[methyl group]] to the [[cytosine]] [[pyrimidine]] ring or [[adenine]] [[purine]] ring.<sup>[[Adrenocortical carcinoma pathophysiology#cite note-pmid25111790-24|[24]]]</sup>
-* Dysregulation in this process is observed in [[Tumor cell|tumor cells.]]
-* A recent study revealed [[Methylation|hypermethylation]] of promoters in ACC with correlation to poor survival and identified ''[[H19 (gene)|H19]]'', ''[[PLAGL1]]'', ''[[G0 phase|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 (gene)|H19]]''.
 ==References==