Is IGSF1 Involved in Human Pituitary Tumor Formation?

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 167-198-Hypothalamus-Pituitary Development & Biology
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-167
Fabio Rueda Faucz*1, Anelia Dafinova Horvath2, Paraskevi Xekouki1, Eva Szarek1, Evgenia Gourgari1, Alison Manning3, Isaac Levy1, Emmanouil Saloustros1, Maria V Nesterova1 and Constantine A Stratakis1
1National Institutes of Health (NIH), Bethesda, MD, 2The George Washington University, Washington, DC, 3Brigham and Women's Hospital, Boston, MA
Background: IGSF1 is a membrane glycoprotein highly expressed in the anterior pituitary gland. Mice with a deficiency in Igsf1 show central hypothyroidism and increased body size. Recently, mutations in this gene were found in humans with central hypothyroidism and testicular enlargement [Sun et al, Nat. Genet. 44(12):1375-81, 2012]. Aim of the study: We looked for IGSF1 germline variations in patients with giantism from the NIH data registry and in healthy controls. We also looked for the expression of IGSF1 in growth hormone (GH)-producing adenomas.  Patients and methods:  We sequenced 11 patients with giantism (GH secreting) and 92 health individuals (100% White Americans) for IGSF1 germline mutations. Immunohistochemistry for IGSF1 was performed in sections from three GH-producing adenomas and in normal pituitary. Results:  In 1 out of 11 patients we identified the sequence variant p.Asn604Tre (c.1811A>C), which by in silico analysis is potentially destructive. The same variation, however, was found in 2 of our controls. We also identified 29 more variations in a total of 18 healthy individuals (16.85%) (3 nonsense, 3 frameshifts and 25 missense), but only 4 of them have been described previously. Immunohistochemistry showed variable IGSF1 staining in the GH-producing tumor from the patient with the IGSF1 mutation compared to a GH-producing tumor from a patient negative for IGSF1 mutations and to a normal control. Conclusions: IGSF1 gene appears quite polymorphic. The mutation identified in one of our patients with giantism was also detected in healthy controls. The increased expression of IGSF1 in patients with an IGSF1 germline mutation may indicate that IGSF1 does not have a causative role in pituitary tumor development but may work as a modifier during oncogenesis.

Nothing to Disclose: FRF, ADH, PX, ES, EG, AM, IL, ES, MVN, CAS

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