Taylor C Brown1, C Christofer Juhlin2, James M Healy1, Adam Stenman3, Jill C Rubinstein1, Reju Korah1, Tobias Carling4. 1. Department of Surgery & Yale Endocrine Neoplasia Laboratory, Yale University School of Medicine, New Haven, CT. 2. Department of Surgery & Yale Endocrine Neoplasia Laboratory, Yale University School of Medicine, New Haven, CT; Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. 3. Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. 4. Department of Surgery & Yale Endocrine Neoplasia Laboratory, Yale University School of Medicine, New Haven, CT. Electronic address: tobias.carling@yale.edu.
Abstract
BACKGROUND: Overexpression of Solute carrier family 12 member 7 (SLC12A7) promotes tumor aggressiveness in various cancers. Previous studies have identified the 5p15.33 region, containing the SLC12A7 locus, as being amplified frequently in adrenocortical carcinoma (ACC). Copy number amplifications (CNAs) may alter gene expression levels and occur frequently in ACC; however, SLC12A7 gene amplifications or expression levels have not been studied in ACC. METHODS: Fifty-five cases of clinically well-characterized ACCs were recruited for this study. Whole-exome sequencing was used to predict CNAs in 19 samples. CNA analysis was performed on an expanded cohort of 26 samples with the use of TaqMan Copy Number Assays. SLC12A7 mRNA expression was analyzed in 32 samples with real-time quantitative polymerase chain reaction and protein expression was assessed by immunohistochemistry. SLC12A7 CNAs and expression patterns were evaluated for correlation with patient and tumor characteristics. RESULTS: Whole-exome sequencing and TaqMan Copy Number Assays demonstrated SLC12A7 amplifications in 68.4% and 65.4% of ACCs tested, respectively. Furthermore, SLC12A7 copy gains were associated with increased gene expression (P < .05) and non-functional tumors (P < .05). SLC12A7 gene expression levels were increased in ACCs compared with normal adrenal tissue (P < .05). CONCLUSION: SLC12A7 gene amplification and overexpression occurs frequently in ACCs and may represent a novel molecular event associated with ACC.
BACKGROUND: Overexpression of Solute carrier family 12 member 7 (SLC12A7) promotes tumor aggressiveness in various cancers. Previous studies have identified the 5p15.33 region, containing the SLC12A7 locus, as being amplified frequently in adrenocortical carcinoma (ACC). Copy number amplifications (CNAs) may alter gene expression levels and occur frequently in ACC; however, SLC12A7 gene amplifications or expression levels have not been studied in ACC. METHODS: Fifty-five cases of clinically well-characterized ACCs were recruited for this study. Whole-exome sequencing was used to predict CNAs in 19 samples. CNA analysis was performed on an expanded cohort of 26 samples with the use of TaqMan Copy Number Assays. SLC12A7 mRNA expression was analyzed in 32 samples with real-time quantitative polymerase chain reaction and protein expression was assessed by immunohistochemistry. SLC12A7 CNAs and expression patterns were evaluated for correlation with patient and tumor characteristics. RESULTS: Whole-exome sequencing and TaqMan Copy Number Assays demonstrated SLC12A7 amplifications in 68.4% and 65.4% of ACCs tested, respectively. Furthermore, SLC12A7 copy gains were associated with increased gene expression (P < .05) and non-functional tumors (P < .05). SLC12A7 gene expression levels were increased in ACCs compared with normal adrenal tissue (P < .05). CONCLUSION:SLC12A7 gene amplification and overexpression occurs frequently in ACCs and may represent a novel molecular event associated with ACC.
Authors: Stan Sidhu; Deborah J Marsh; George Theodosopoulos; Jeanette Philips; Christopher P Bambach; Peter Campbell; Christopher J Magarey; Colin F J Russell; Klaus-Martin Schulte; Hans-Dietrich Röher; Leigh Delbridge; Bruce G Robinson Journal: J Clin Endocrinol Metab Date: 2002-07 Impact factor: 5.958
Authors: M Kjellman; O P Kallioniemi; R Karhu; A Höög; L O Farnebo; G Auer; C Larsson; M Bäckdahl Journal: Cancer Res Date: 1996-09-15 Impact factor: 12.701
Authors: Joyce Y Cheng; Taylor C Brown; Timothy D Murtha; Adam Stenman; C Christofer Juhlin; Catharina Larsson; James M Healy; Manju L Prasad; Wolfram T Knoefel; Andreas Krieg; Ute I Scholl; Reju Korah; Tobias Carling Journal: BMC Cancer Date: 2017-03-01 Impact factor: 4.430
Authors: Taylor C Brown; Timothy D Murtha; Jill C Rubinstein; Reju Korah; Tobias Carling Journal: Cell Commun Signal Date: 2018-06-08 Impact factor: 5.712