title: Whole-exome sequencing identifies variants in invasive pituitary adenomas.
abstract: Pituitary adenomas exhibit a wide range of behaviors. The prediction of invasion or malignant behavior in pituitary adenomas remains challenging. The objective of the present study was to identify the genetic abnormalities associated with invasion in sporadic pituitary adenomas. In the present study, the exomes of six invasive pituitary adenomas (IPA) and six non-invasive pituitary adenomas (nIPA) were sequenced by whole-exome sequencing. Variants were confirmed by dideoxynucleotide sequencing, and candidate driver genes were assessed in an additional 28 pituitary adenomas. A total of 15 identified variants were mainly associated with angiogenesis, metabolism, cell cycle phase, cellular component organization, cytoskeleton and biogenesis immune at a cellular level, including 13 variants that occurred as single nucleotide variants and 2 that comprised of insertions. The messenger RNA (mRNA) levels of diffuse panbronchiolitis critical region 1 (DPCR1), KIAA0226, myxovirus (influenza virus) resistance, proline-rich protein BstNI subfamily 3, PR domain containing 2, with ZNF domain, RIZ1 (PRDM2), PR domain containing 8 (PRDM8), SPANX family member N2 (SPANXN2), TRIO and F-actin binding protein and zinc finger protein 717 in IPA specimens were 50% decreased compared with nIPA specimens. In particular, DPCR1, PRDM2, PRDM8 and SPANXN2 mRNA levels in IPA specimens were approximately four-fold lower compared with nIPA specimens (P=0.003, 0.007, 0.009 and 0.004, respectively). By contrast, the mRNA levels of dentin sialophospho protein, EGF like domain, multiple 7 (EGFL7), low density lipoprotein receptor-related protein 1B and dynein, axonemal, assembly factor 1 (LRRC50) were increased in IPA compared with nIPA specimens (P=0.041, 0.037, 0.022 and 0.013, respectively). Furthermore, decreased PRDM2 expression was associated with tumor recurrence. The findings of the present study indicate that DPCR1, EGFL7, the PRDM family and LRRC50 in pituitary adenomas are modifiers of tumorigenesis, and most likely contribute to the development of oncocytic change and to the invasive tumor phenotype.
authors.affiliation: Key Laboratory of Central Nervous System Injury Research, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China; Department of Neurosurgery, The Affiliated Hospital of Medical College, Qingdao University, Qingdao, Shandong 266071, P.R. China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Lan
authors.affiliation: Key Laboratory of Central Nervous System Injury Research, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Gao
authors.affiliation: Department of Neurosurgery, Provincial Hospital Affiliated to Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Key Laboratory of Central Nervous System Injury Research, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Feng
authors.affiliation: Key Laboratory of Central Nervous System Injury Research, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China.
authors.forename: Jiwei
authors.initials: J
authors.lastname: Bai
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 200050, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Central Nervous System Injury Research, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cao
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 200050, P.R. China.
authors.forename: Songbai
authors.initials: S
authors.lastname: Gui
authors.affiliation: Key Laboratory of Central Nervous System Injury Research, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Gong
authors.affiliation: Key Laboratory of Central Nervous System Injury Research, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China.
authors.forename: Yazhuo
authors.initials: Y
authors.lastname: Zhang
keywords: PR domain family; exome sequencing; invasive; pituitary adenomas; variant