PMID- 25763608
OWN - NLM
STAT- MEDLINE
DCOM- 20150930
LR  - 20150509
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Linking)
VI  - 100
IP  - 5
DP  - 2015 May
TI  - Frequency and clinical correlates of somatic Ying Yang 1 mutations in sporadic 
      insulinomas.
PG  - E776-82
LID - 10.1210/jc.2015-1100 [doi]
AB  - CONTEXT: Insulinomas represent pancreatic neuroendocrine neoplasms that cause 
      severe morbidity attributed to their often pronounced endocrine activity. Apart 
      from hereditary forms such as multiple endocrine neoplasia type 1 (MEN-1), 
      genetic causes for sporadic insulinoma development had remained obscure until 
      recently. Applying next-generation sequencing methods, disease-causing genetic 
      alterations have been identified in various endocrine tumors. OBJECTIVE AND 
      DESIGN: Paired tumor and blood DNA from eight patients with sporadic insulinomas 
      (five females and two malignant tumors) were analyzed by whole-exome sequencing. 
      After this initial analysis, Ying Yang 1 (YY1) mutation status was assessed in a 
      larger cohort of 39 additional insulinomas (including eight malignant and one 
      liver metastasis) from three German hospitals by targeted sequencing. The 
      mutation status was correlated with various clinical parameters. RESULTS: A range 
      of one to 12 somatic genetic variants were identified by exome sequencing. A 
      recurrent somatic Thr372Arg YY1 point mutation was detected in two patients of 
      the initial cohort and four patients of the second cohort (total, six of 47; 
      13%). The presence of the mutation was associated with a trend toward higher age 
      (63.5 y; IQR, 48.0-74.0 vs 45.0 y; IQR, 33.0-63.0; P = .05), and all affected 
      patients were females (six of six; P = .04). All other clinical parameters, 
      including the presence of malignancy and metastatic spread, tumor localization, 
      and hypoglycemic episodes were not different between YY1-mutated and nonmutated 
      tumor carriers. CONCLUSIONS: The somatic Thr372Arg YY1 mutation is a relevant 
      finding in female patients with sporadic insulinomas. The prevalence of this 
      mutation in this Caucasian population is considerably lower compared to that of a 
      recently described Asian cohort.
FAU - Lichtenauer, Urs D
AU  - Lichtenauer UD
AD  - Medizinische Klinik und Poliklinik IV (U.D.L., G.D.D., M.R., F.B.), Klinikum der 
      Universitat Munchen, 80336 Munich, Germany; Department of Visceral, Thoracic, and 
      Vascular Surgery (E.P.S., D.W., D.K.B.), University Hospital Giessen and Marburg 
      GmbH, 35043 Marburg, Germany; Institute of Human Genetics (T.W., A.S., T.S., 
      S.D., T.M., T.M.S.), Helmholtz Zentrum Munchen, 85764 Neuherberg, Germany; 
      Funktionsbereich Spezielle Endokrinologie (A.K., M.S.), Universitatsklinikum 
      Dusseldorf, 40225 Dusseldorf Germany; Biobank (under the administration of the 
      Human Tissue and Cell Research) Foundation (W.E.T.), Department of General, 
      Visceral, Transplantation, Vascular and Thoracic Surgery, Hospital of the 
      University of Munich, 81377 Munich, Germany; Germany Institute of Human Genetics 
      (T.M., T.M.S.), Technische Universitat Munchen, 81675 Munich, Germany; German 
      Centre for Cardiovascular Research Partner Site (T.M., T.M.S.), Munich Heart 
      Alliance, 80802 Munich, Germany; Department of Medicine I (M.F.), Endocrine and 
      Diabetes Unit, University Hospital, University of Wurzburg, 97080 Wurzburg, 
      Germany; and Comprehensive Cancer Center Mainfranken (M.F.), University of 
      Wurzburg, 97080 Wurzburg, Germany.
FAU - Di Dalmazi, Guido
AU  - Di Dalmazi G
FAU - Slater, Emily P
AU  - Slater EP
FAU - Wieland, Thomas
AU  - Wieland T
FAU - Kuebart, Anne
AU  - Kuebart A
FAU - Schmittfull, Anett
AU  - Schmittfull A
FAU - Schwarzmayr, Thomas
AU  - Schwarzmayr T
FAU - Diener, Susanne
AU  - Diener S
FAU - Wiese, Dominik
AU  - Wiese D
FAU - Thasler, Wolfgang E
AU  - Thasler WE
FAU - Reincke, Martin
AU  - Reincke M
FAU - Meitinger, Thomas
AU  - Meitinger T
FAU - Schott, Matthias
AU  - Schott M
FAU - Fassnacht, Martin
AU  - Fassnacht M
FAU - Bartsch, Detlef K
AU  - Bartsch DK
FAU - Strom, Tim M
AU  - Strom TM
FAU - Beuschlein, Felix
AU  - Beuschlein F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150312
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (YY1 Transcription Factor)
RN  - 0 (YY1 protein, human)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Exome
MH  - Female
MH  - Humans
MH  - Insulinoma/*genetics/pathology
MH  - Male
MH  - Middle Aged
MH  - *Mutation
MH  - Pancreatic Neoplasms/*genetics/pathology
MH  - YY1 Transcription Factor/*genetics
EDAT- 2015/03/13 06:00
MHDA- 2015/10/01 06:00
CRDT- 2015/03/13 06:00
PHST- 2015/03/13 06:00 [entrez]
PHST- 2015/03/13 06:00 [pubmed]
PHST- 2015/10/01 06:00 [medline]
AID - 10.1210/jc.2015-1100 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2015 May;100(5):E776-82. doi: 10.1210/jc.2015-1100. Epub 
      2015 Mar 12.