BACKGROUND: Approximately 60% of sporadic medullary thyroid carcinomas (sMTC) remain orphan of a recognized genetic cause. Recently, a high percentage of RAS point mutations have been described in RET-negative sMTC. The aim of this study was to assess the prevalence of RAS point mutations in a large series of MTC collected in four Italian centers. METHODS: For this purpose, we studied codons 12, 13, and 61 of H-, K-, and N-RAS genes in 188 MTC samples, either hereditary or sporadic, by direct sequencing. Correlations between the RAS mutational status and the clinical-pathological features of MTC patients as well as a meta-analysis of all published data were performed. RESULTS: The prevalence of RAS mutations in the present series of MTC was 10.1%, and 17.6% when considering only RET-negative cases. RAS mutations were found in MTC tumoral tissue, but not in peripheral blood indicating their somatic origin. A novel mutation in codon 72 (M72I) was found, but with a low or null transforming potential. No association was found between the presence of RAS mutations and the clinical-pathological features of the patients. Although not statistically significant, a positive association between the presence of RAS mutations and a better outcome was observed. The meta-analysis of all published studies confirmed a prevalence of 8.8% for RAS mutations in MTC. CONCLUSIONS: The prevalence of RAS mutations in our MTC series was relatively low and consistent with the meta-analysis data. Only somatic RAS mutations were found and only in RET-negative sMTC. Likewise, MTCs that harbor a RAS mutation identify a subgroup of tumors with less aggressive behavior. To our knowledge, this is the largest series of MTCs studied for the presence of mutations in RAS genes and the first meta-analysis on this specific topic.
BACKGROUND: Approximately 60% of sporadic medullary thyroid carcinomas (sMTC) remain orphan of a recognized genetic cause. Recently, a high percentage of RAS point mutations have been described in RET-negative sMTC. The aim of this study was to assess the prevalence of RAS point mutations in a large series of MTC collected in four Italian centers. METHODS: For this purpose, we studied codons 12, 13, and 61 of H-, K-, and N-RAS genes in 188 MTC samples, either hereditary or sporadic, by direct sequencing. Correlations between the RAS mutational status and the clinical-pathological features of MTC patients as well as a meta-analysis of all published data were performed. RESULTS: The prevalence of RAS mutations in the present series of MTC was 10.1%, and 17.6% when considering only RET-negative cases. RAS mutations were found in MTC tumoral tissue, but not in peripheral blood indicating their somatic origin. A novel mutation in codon 72 (M72I) was found, but with a low or null transforming potential. No association was found between the presence of RAS mutations and the clinical-pathological features of the patients. Although not statistically significant, a positive association between the presence of RAS mutations and a better outcome was observed. The meta-analysis of all published studies confirmed a prevalence of 8.8% for RAS mutations in MTC. CONCLUSIONS: The prevalence of RAS mutations in our MTC series was relatively low and consistent with the meta-analysis data. Only somatic RAS mutations were found and only in RET-negative sMTC. Likewise, MTCs that harbor a RAS mutation identify a subgroup of tumors with less aggressive behavior. To our knowledge, this is the largest series of MTCs studied for the presence of mutations in RAS genes and the first meta-analysis on this specific topic.
Authors: Elizabeth G Grubbs; Patrick Kwok-Shing Ng; Jacquelin Bui; Naifa L Busaidy; Ken Chen; Jeffrey E Lee; Xinyan Lu; Hengyu Lu; Funda Meric-Bernstam; Gordon B Mills; Gary Palmer; Nancy D Perrier; Kenneth L Scott; Kenna R Shaw; Steven G Waguespack; Michelle D Williams; Roman Yelensky; Gilbert J Cote Journal: J Clin Endocrinol Metab Date: 2014-12-29 Impact factor: 5.958
Authors: Samuel A Wells; Sylvia L Asa; Henning Dralle; Rossella Elisei; Douglas B Evans; Robert F Gagel; Nancy Lee; Andreas Machens; Jeffrey F Moley; Furio Pacini; Friedhelm Raue; Karin Frank-Raue; Bruce Robinson; M Sara Rosenthal; Massimo Santoro; Martin Schlumberger; Manisha Shah; Steven G Waguespack Journal: Thyroid Date: 2015-06 Impact factor: 6.568
Authors: Mosin S Khan; Arshad A Pandith; Mahboob Ul Hussain; Mohammad Iqbal; Nighat P Khan; Khurshid A Wani; Shariq R Masoodi; Syed Mudassar Journal: Tumour Biol Date: 2012-11-13