RET
小结
RET是致癌基因，编码蛋白是一种受体酪氨酸激酶， 其可与神经胶质细胞系衍生的神经营养因子（GDNF）家族的配体结合，并通过促癌基因丝裂原活化蛋白激酶（MAPK）和磷酸肌醇3-激酶（PI3K）途径传递细胞内信号。RET通常在发育的胚胎中表达，在神经和神经内分泌谱系中起着特别重要的作用。RET胚系激活突变与多发性内分泌腺癌2A型（MEN2A：甲状腺髓样癌，嗜铬细胞瘤，甲状旁腺功能亢进）的发生相关。在癌症中，RET可以通过点突变或基因重排与多种易位配偶体激活，产生组成型活性胞质癌蛋白。已经在多种癌症中发现RET的多种突变类型，包括乳头状甲状腺癌，肺腺癌和慢性髓单核细胞白血病（CMML）。此外，野生型RET的异常表达或活化与胰腺癌中的肿瘤侵袭和转移以及乳腺癌中的内分泌治疗抗性相关。
RET is a receptor tyrosine kinase that binds ligands of the glial cell line-derived neurotrophic factor (GDNF) family and transmits intracellular signals via the pro-oncogenic mitogen activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) pathways. RET is normally expressed in the developing embryo, playing a particularly important role in neural and neuroendocrine lineages. In cancer, RET can be activated either through point mutations or gene rearrangements with a variety of translocation partners resulting in constitutively active cytosolic oncoproteins. Heritable activating mutations in RET lead to the highly penetrant familial cancer syndromes multiple endocrine neoplasia type 2A (MEN2A: medullary thyroid carcinoma, pheochromocytoma, hyperparathyroidism), multiple endocrine neoplasia type 2B (MEN2B: medullary thyroid carcinoma, pheochromocytoma, multiple mucosal neuromas and intestinal ganglioneuromas, marfanoid habitus) and familial medullary thyroid carcinoma (FMTC). Oncogenic somatic mutations include point mutations and genomic rearrangements of the RET locus leading to inversions or translocations. These have been identified in various cancers including papillary thyroid cancer, lung adenocarcinoma and chronic myelomonocytic leukemia (CMML). In addition, aberrant expression or activation of wildtype RET correlates with tumor invasion and metastasis in pancreatic cancer and endocrine therapy resistance in breast cancer.