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Next-generation sequencing of adrenocortical carcinoma reveals new routes to targeted therapies.

Ross JS, Wang K, Rand JV, Gay L, Presta MJ, Sheehan CE, Ali SM, Elvin JA, Labrecque E, Hiemstra C, Buell J, Otto GA, Yelensky R, Lipson D, Morosini D, Chmielecki J, Miller VA, Stephens PJ - J. Clin. Pathol. (2014)

Bottom Line: At least one GA was found in 22 (76%) ACC (mean 2.6 alterations per ACC).The most frequent GAs were in TP53 (34%), NF1 (14%), CDKN2A (14%), MEN1 (14%), CTNNB1 (10%) and ATM (10%).APC, CCND2, CDK4, DAXX, DNMT3A, KDM5C, LRP1B, MSH2 and RB1 were each altered in two cases (7%) and EGFR, ERBB4, KRAS, MDM2, NRAS, PDGFRB, PIK3CA, PTEN and PTCH1 were each altered in a single case (3%).

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York, USA Foundation Medicine, Inc., Cambridge, Massachusetts, USA.

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Tile plot of genomic alterations identified in 29 adrenocortical carcinoma cases.
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JCLINPATH2014202514F1: Tile plot of genomic alterations identified in 29 adrenocortical carcinoma cases.

Mentions: A total of 76 alterations were identified (25 base substitutions and short indels, 14 gene amplifications, 7 gene homozygous deletions and 30 gene truncations) in 43 genes, with 22 cases (76%) harbouring at least one alteration, for a mean of 2.6 alterations per tumour (table 2, figure 1). No gene fusions were identified. The most common biologically relevant alterations that cannot currently be linked to a targeted treatment option were found in TP53 (34%), MEN1 (14%) CTNNB1 (10%), APC (7%), DAXX (7%), KDM5C (7%), LRP1B (7%), MSH2 (7%) and RB1 (7%). At least one clinically meaningful alteration that could potentially guide decisions for targeted treatment was found in 59% (17/29) of the ACC cases. The most common potentially actionable alterations involved NF1 (14%), CDKN2A (14%), ATM (10%), CCND2 (7%), CDK4 (7%), DNMT3A (7%) with EGFR, ERBB4, KRAS, MDM2, NRAS, PDGFRB, PIK3CA, PTEN, PTCH1 and STK11, each altered in a single case. There were no observable differences in the pattern of GAs of the ACC where the primary tumour was sequenced compared with ACC where a metastasis sample was used.


Next-generation sequencing of adrenocortical carcinoma reveals new routes to targeted therapies.

Ross JS, Wang K, Rand JV, Gay L, Presta MJ, Sheehan CE, Ali SM, Elvin JA, Labrecque E, Hiemstra C, Buell J, Otto GA, Yelensky R, Lipson D, Morosini D, Chmielecki J, Miller VA, Stephens PJ - J. Clin. Pathol. (2014)

Tile plot of genomic alterations identified in 29 adrenocortical carcinoma cases.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4215283&req=5

JCLINPATH2014202514F1: Tile plot of genomic alterations identified in 29 adrenocortical carcinoma cases.
Mentions: A total of 76 alterations were identified (25 base substitutions and short indels, 14 gene amplifications, 7 gene homozygous deletions and 30 gene truncations) in 43 genes, with 22 cases (76%) harbouring at least one alteration, for a mean of 2.6 alterations per tumour (table 2, figure 1). No gene fusions were identified. The most common biologically relevant alterations that cannot currently be linked to a targeted treatment option were found in TP53 (34%), MEN1 (14%) CTNNB1 (10%), APC (7%), DAXX (7%), KDM5C (7%), LRP1B (7%), MSH2 (7%) and RB1 (7%). At least one clinically meaningful alteration that could potentially guide decisions for targeted treatment was found in 59% (17/29) of the ACC cases. The most common potentially actionable alterations involved NF1 (14%), CDKN2A (14%), ATM (10%), CCND2 (7%), CDK4 (7%), DNMT3A (7%) with EGFR, ERBB4, KRAS, MDM2, NRAS, PDGFRB, PIK3CA, PTEN, PTCH1 and STK11, each altered in a single case. There were no observable differences in the pattern of GAs of the ACC where the primary tumour was sequenced compared with ACC where a metastasis sample was used.

Bottom Line: At least one GA was found in 22 (76%) ACC (mean 2.6 alterations per ACC).The most frequent GAs were in TP53 (34%), NF1 (14%), CDKN2A (14%), MEN1 (14%), CTNNB1 (10%) and ATM (10%).APC, CCND2, CDK4, DAXX, DNMT3A, KDM5C, LRP1B, MSH2 and RB1 were each altered in two cases (7%) and EGFR, ERBB4, KRAS, MDM2, NRAS, PDGFRB, PIK3CA, PTEN and PTCH1 were each altered in a single case (3%).

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York, USA Foundation Medicine, Inc., Cambridge, Massachusetts, USA.

Show MeSH
Related in: MedlinePlus