Next-generation sequencing of adrenocortical carcinoma reveals new routes to targeted therapies.
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%).
Affiliation: Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York, USA Foundation Medicine, Inc., Cambridge, Massachusetts, USA.Show MeSH
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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.
Affiliation: Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York, USA Foundation Medicine, Inc., Cambridge, Massachusetts, USA.