CONTEXT: The tumorigenic role of genetic abnormalities in sporadic pituitary nonfunctioning adenomas (NFAs), which usually originate from gonadotroph cells, is unknown. OBJECTIVE: The objective of the study was to identify somatic genetic abnormalities in sporadic pituitary NFAs. DESIGN: Whole-exome sequencing was performed using DNA from 7 pituitary NFAs and leukocyte samples obtained from the same patients. Somatic variants were confirmed by dideoxynucleotide sequencing, and candidate driver genes were assessed in an additional 24 pituitary NFAs. RESULTS: Whole-exome sequencing achieved a high degree of coverage such that approximately 97% of targeted bases were represented by more than 10 base reads; 24 somatic variants were identified and confirmed in the discovery set of 7 pituitary NFAs (mean 3.5 variants/tumor; range 1-7). Approximately 80% of variants occurred as missense single nucleotide variants and the remainder were synonymous changes or small frameshift deletions. Each of the 24 mutations occurred in independent genes with no recurrent mutations. Mutations were not observed in genes previously associated with pituitary tumorigenesis, although somatic variants in putative driver genes including platelet-derived growth factor D (PDGFD), N-myc down-regulated gene family member 4 (NDRG4), and Zipper sterile-α-motif kinase (ZAK) were identified; however, DNA sequence analysis of these in the validation set of 24 pituitary NFAs did not reveal any mutations indicating that these genes are unlikely to contribute significantly in the etiology of sporadic pituitary NFAs. CONCLUSIONS: Pituitary NFAs harbor few somatic mutations consistent with their low proliferation rates and benign nature, but mechanisms other than somatic mutation are likely involved in the etiology of sporadic pituitary NFAs.
CONTEXT: The tumorigenic role of genetic abnormalities in sporadic pituitary nonfunctioning adenomas (NFAs), which usually originate from gonadotroph cells, is unknown. OBJECTIVE: The objective of the study was to identify somatic genetic abnormalities in sporadic pituitary NFAs. DESIGN: Whole-exome sequencing was performed using DNA from 7 pituitary NFAs and leukocyte samples obtained from the same patients. Somatic variants were confirmed by dideoxynucleotide sequencing, and candidate driver genes were assessed in an additional 24 pituitary NFAs. RESULTS: Whole-exome sequencing achieved a high degree of coverage such that approximately 97% of targeted bases were represented by more than 10 base reads; 24 somatic variants were identified and confirmed in the discovery set of 7 pituitary NFAs (mean 3.5 variants/tumor; range 1-7). Approximately 80% of variants occurred as missense single nucleotide variants and the remainder were synonymous changes or small frameshift deletions. Each of the 24 mutations occurred in independent genes with no recurrent mutations. Mutations were not observed in genes previously associated with pituitary tumorigenesis, although somatic variants in putative driver genes including platelet-derived growth factor D (PDGFD), N-myc down-regulated gene family member 4 (NDRG4), and Zipper sterile-α-motif kinase (ZAK) were identified; however, DNA sequence analysis of these in the validation set of 24 pituitary NFAs did not reveal any mutations indicating that these genes are unlikely to contribute significantly in the etiology of sporadic pituitary NFAs. CONCLUSIONS: Pituitary NFAs harbor few somatic mutations consistent with their low proliferation rates and benign nature, but mechanisms other than somatic mutation are likely involved in the etiology of sporadic pituitary NFAs.
Authors: Yuchen Jiao; Chanjuan Shi; Barish H Edil; Roeland F de Wilde; David S Klimstra; Anirban Maitra; Richard D Schulick; Laura H Tang; Christopher L Wolfgang; Michael A Choti; Victor E Velculescu; Luis A Diaz; Bert Vogelstein; Kenneth W Kinzler; Ralph H Hruban; Nickolas Papadopoulos Journal: Science Date: 2011-01-20 Impact factor: 47.728
Authors: Pengyuan Liu; Carl Morrison; Liang Wang; Donghai Xiong; Peter Vedell; Peng Cui; Xing Hua; Feng Ding; Yan Lu; Michael James; John D Ebben; Haiming Xu; Alex A Adjei; Karen Head; Jaime W Andrae; Michael R Tschannen; Howard Jacob; Jing Pan; Qi Zhang; Francoise Van den Bergh; Haijie Xiao; Ken C Lo; Jigar Patel; Todd Richmond; Mary-Anne Watt; Thomas Albert; Rebecca Selzer; Marshall Anderson; Jiang Wang; Yian Wang; Sandra Starnes; Ping Yang; Ming You Journal: Carcinogenesis Date: 2012-04-17 Impact factor: 4.944
Authors: Veerle Melotte; Marjolein H F M Lentjes; Sandra M van den Bosch; Debby M E I Hellebrekers; Joep P J de Hoon; Kim A D Wouters; Kathleen L J Daenen; Iris E J M Partouns-Hendriks; Filip Stessels; Joost Louwagie; Kim M Smits; Matty P Weijenberg; Silvia Sanduleanu; Carolina A J Khalid-de Bakker; Frank A Oort; Gerrit A Meijer; Daisy M A E Jonkers; James G Herman; Adriaan P de Bruïne; Manon van Engeland Journal: J Natl Cancer Inst Date: 2009-06-17 Impact factor: 13.506
Authors: R M Ruggeri; L Santarpia; L Curtò; M L Torre; M Galatioto; S Galatioto; F Trimarchi; S Cannavò Journal: J Endocrinol Invest Date: 2008-11 Impact factor: 4.256
Authors: Sunita M C De Sousa; Paul P S Wang; Stephen Santoreneos; Angeline Shen; Christopher J Yates; Milena Babic; Leila Eshraghi; Jinghua Feng; Barbara Koszyca; Samuel Roberts-Thomson; Andreas W Schreiber; David J Torpy; Hamish S Scott Journal: Endocr Pathol Date: 2019-12 Impact factor: 3.943
Authors: Scott Haston; Sara Pozzi; Gabriela Carreno; Saba Manshaei; Leonidas Panousopoulos; Jose Mario Gonzalez-Meljem; John R Apps; Alex Virasami; Selvam Thavaraj; Alice Gutteridge; Tim Forshew; Richard Marais; Sebastian Brandner; Thomas S Jacques; Cynthia L Andoniadou; Juan Pedro Martinez-Barbera Journal: Development Date: 2017-05-15 Impact factor: 6.868
Authors: Ashley B Grossman; Shereen Ezzat; Sylvia L Asa; Ozgur Mete; Michael D Cusimano; Ian E McCutcheon; Arie Perry; Shozo Yamada; Hiroshi Nishioka; Olivera Casar-Borota; Silvia Uccella; Stefano La Rosa Journal: Mod Pathol Date: 2021-05-21 Impact factor: 7.842