Somatic alterations of CDKN1B are associated with small bowel neuroendocrine tumors

• Published in: Cancer genetics Vol. 208; no. 11; pp. 564 - 570
• Main Authors: Maxwell, Jessica E, Sherman, Scott K, Li, Guiying, Choi, Allen B, Bellizzi, Andrew M, O'Dorisio, Thomas M, Howe, James R
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2015
• Subjects: CDKN1B; frameshift mutation; Hematology, Oncology and Palliative Medicine; Medical Education; Neuroendocrine tumor; p27; pancreatic neuroendocrine tumor; small bowel neuroendocrine tumor; CDKN1B; p27; Neuroendocrine tumor; small bowel neuroendocrine tumor; frameshift mutation; pancreatic neuroendocrine tumor
• ISSN: 2210-7762; 2210-7770
• DOI: 10.1016/j.cancergen.2015.08.003

CDKN1B , a cyclin-dependent kinase inhibitor associated with G1 arrest, was recently proposed as an important tumor suppressor gene in small bowel neuroendocrine tumors (SBNETs). The rate of frameshift mutations in SBNET primaries are reportedly 7.4%, and hemizygous deletions are 6.7%. We set out to confirm the role of CDKN1B mutations and copy number variants (CNVs) in primary SBNETs, and whether these are also found in pancreatic neuroendocrine tumors (PNETs). Genomic DNA was isolated from 90 primary SBNETs and 67 PNETs. Coding exons of CDKN1B were amplified by PCR and sequenced. CNV analysis was performed by quantitative PCR, p27 expression was evaluated using immunohistochemistry. In SBNETS, three frameshifts, one missense mutation, and three CNVs were observed. The total rate of CDKN1B alterations was 7.0% (6 of 86; 95% confidence interval (CI) 3.2-4.4%). The frameshift rate was 3.5% (95% CI 1.1-9.8%). One SBNET patient had a hemizygous deletion of CDKN1B , and two patients had duplications (3.4%; 95% CI −0.41-7.2%). One PNET patient had a duplication, and two patients had hemizygous deletions (4.8%; 95% CI −0.44-10%). Alterations of cell-cycle control due to alterations in CDKN1B may be one mechanism by which SBNETs develop, which could have implications for new treatment modalities.