BACKGROUND: Structural genetic changes of tumor suppressor genes MTS-1/INK4A and MTS-2/INK4B were demonstrated in a variety of human cancers but not in thyroid cancer until now. METHODS: Because MTS-2 encodes the tumor suppressor p15, a protein related to the transforming growth factor-beta inhibition of many epithelial cells such as thyrocytes, we investigated MTS-1 and MTS-2 genes in 87 thyroid cancers (29 papillary, 26 follicular, 31 medullary, and 1 anaplastic), 8 goiters, and 38 control DNAs by using a semiquantitative polymerase chain reaction technique. RESULTS: We failed to demonstrate homozygous deletions of MTS-1 and MTS-2 in thyroid tumors, but we demonstrated a highly frequent base pair exchange of the MTS-2 gene 27 codons upstream the 5' end of exon 2. This genetic change formerly described as polymorphism was found to a lesser degree (15%), in control DNA when compared with papillary thyroid cancer and medullary thyroid cancer (35% and 32%, respectively), and it paralleled a higher prevalence of extensive lymph node metastases in thyroid cancer (p < 0.01). In addition, we could demonstrate that genetic changes at site 27 upstream the 5' end of exon 2 were harbored as somatic mutations in 2 of 10 thyroid cancers with simultaneously investigated corresponding control tissue. CONCLUSIONS: We conclude that base pair exchange at this site most likely has biologic importance for the tumor suppressor p15 and may contribute to tumorigenesis and lymphatic spread of differentiated and medullary thyroid cancer.
BACKGROUND: Structural genetic changes of tumor suppressor genes MTS-1/INK4A and MTS-2/INK4B were demonstrated in a variety of humancancers but not in thyroid cancer until now. METHODS: Because MTS-2 encodes the tumor suppressorp15, a protein related to the transforming growth factor-beta inhibition of many epithelial cells such as thyrocytes, we investigated MTS-1 and MTS-2 genes in 87 thyroid cancers (29 papillary, 26 follicular, 31 medullary, and 1 anaplastic), 8 goiters, and 38 control DNAs by using a semiquantitative polymerase chain reaction technique. RESULTS: We failed to demonstrate homozygous deletions of MTS-1 and MTS-2 in thyroid tumors, but we demonstrated a highly frequent base pair exchange of the MTS-2 gene 27 codons upstream the 5' end of exon 2. This genetic change formerly described as polymorphism was found to a lesser degree (15%), in control DNA when compared with papillary thyroid cancer and medullary thyroid cancer (35% and 32%, respectively), and it paralleled a higher prevalence of extensive lymph node metastases in thyroid cancer (p < 0.01). In addition, we could demonstrate that genetic changes at site 27 upstream the 5' end of exon 2 were harbored as somatic mutations in 2 of 10 thyroid cancers with simultaneously investigated corresponding control tissue. CONCLUSIONS: We conclude that base pair exchange at this site most likely has biologic importance for the tumor suppressorp15 and may contribute to tumorigenesis and lymphatic spread of differentiated and medullary thyroid cancer.
Authors: Karine Pozo; Antje Hillmann; Alexander Augustyn; Florian Plattner; Tao Hai; Tanvir Singh; Saleh Ramezani; Xiankai Sun; Roswitha Pfragner; John D Minna; Gilbert J Cote; Herbert Chen; James A Bibb; Fiemu E Nwariaku Journal: Oncotarget Date: 2015-05-20