Departamento de Medicina y Nutrición, División de Ciencias de la Salud, Campus León, Universidad de Guanajuato, Guanajuato, Mexico.
Diagn Pathol. 2012 Jun 7;7:63. doi: 10.1186/1746-1596-7-63.
Association between DNA alterations and clinical parameters as recurrence, survival or prognosis has been found in a variety of tumors. A clear association between Medullary Thyroid Carcinoma (MTC) and RET oncogene mutation has been accepted. Specifically M918T RET mutation represents the main genetic event in most cases of sporadic MTC (SMTC) and limited chromosomal alterations analyses have been performed.
In the present work, a comparative genomic hybridization (CGH) study was performed using DNA from a primary tumor in a M918T RET mutation-positive SMTC patient and from its lymph node metastasis to investigate additional genetic alterations. We studied a patient with 15 years of follow-up and persistence of disease, confirmed by periodical elevated serum calcitonin (CT) levels.
Only 3 chromosomal imbalances were identified in the primary tumor, gain of 18p, and loss of 6p and 16p region, whereas 25 chromosomal imbalances were identified in the metastasis (9 gains and 16 losses).
The chromosomal changes 6p-, 16p-, 18p + could determine in part the oncogenic phenotype in the primary M918T RET positive tumor and probably related to persistence of high serum CT levels in this patient. The additional chromosomal changes observed could be related to the metastasis phenotype. We suggest that some genes mapped at 6p, 16p and 18p chromosomal regions, could act as genes associated to cancer and could be related to persistent SMTC and good prognosis.
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1720753793691097.
在各种肿瘤中，已经发现 DNA 改变与复发、生存或预后等临床参数之间存在关联。髓样甲状腺癌 (MTC) 与 RET 癌基因突变之间的明确关联已被接受。具体而言，M918T RET 突变代表了大多数散发性 MTC (SMTC) 的主要遗传事件，并且已经进行了有限的染色体改变分析。
在本工作中，对 M918T RET 突变阳性 SMTC 患者的原发肿瘤及其淋巴结转移中的 DNA 进行了比较基因组杂交 (CGH) 研究，以研究其他遗传改变。我们研究了一位 15 年随访且疾病持续存在的患者，通过定期升高的血清降钙素 (CT) 水平得到证实。
在原发肿瘤中仅发现 3 个染色体不平衡，即 18p 的增益和 6p 和 16p 区域的丢失，而在转移瘤中发现了 25 个染色体不平衡（9 个增益和 16 个丢失）。
6p-、16p-、18p+染色体变化部分决定了 M918T RET 阳性原发肿瘤的致癌表型，并且可能与该患者血清 CT 水平持续升高有关。观察到的额外染色体变化可能与转移表型有关。我们建议，映射到 6p、16p 和 18p 染色体区域的一些基因可能作为与癌症相关的基因起作用，并且可能与持续存在的 SMTC 和良好的预后有关。
