Gailani M R, Bale A E
Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06520, USA.
J Natl Cancer Inst. 1997 Aug 6;89(15):1103-9. doi: 10.1093/jnci/89.15.1103.
Many genes originally identified because of their role in embryonic development are also important in postnatal control of cell growth and differentiation. Mutations in some of these genes have been shown to cause cancer. Basal cell carcinoma (BCC) of the skin is the most common cancer in humans. More than 750000 new cases are diagnosed annually, and the incidence is rising. BCCs are slow-growing, locally invasive tumors that rarely metastasize but can result in extensive morbidity through local recurrence and tissue destruction. Epidemiologic studies suggest that sunlight (particularly UVB radiation) is a strong risk factor for BCC formation, although other factors are also involved. The nevoid basal cell carcinoma syndrome (NBCCS), a rare genetic disorder, is characterized by predisposition to BCCs and other tumors as well as to a wide range of developmental defects. NBCCS maps to chromosome 9q22.3, and loss of heterozygosity at this site in both sporadic and hereditary BCCs suggests that it functions as a tumor suppressor. The gene for NBCCS was recently cloned and is the human homologue of the Drosophila gene "patched." Genetic studies in Drosophila show that patched is part of the hedgehog signaling pathway, which is important in determining embryonic patterning and cell fate in multiple structures of the developing embryo. Human patched is mutated in both hereditary and sporadic BCCs, and inactivation of this gene is probably a necessary, if not sufficient, step for BCC formation. Delineation of the biochemical pathway in which patched functions may lead to rational medical therapy for BCCs and possibly for other tumors associated with NBCCS.
许多最初因其在胚胎发育中的作用而被鉴定的基因，在出生后对细胞生长和分化的控制中也很重要。已表明其中一些基因的突变会导致癌症。皮肤基底细胞癌（BCC）是人类最常见的癌症。每年有超过750000例新病例被诊断出来，且发病率正在上升。BCC是生长缓慢、局部侵袭性的肿瘤，很少发生转移，但可通过局部复发和组织破坏导致广泛的发病率。流行病学研究表明，阳光（尤其是UVB辐射）是BCC形成的一个强大风险因素，尽管也涉及其他因素。痣样基底细胞癌综合征（NBCCS）是一种罕见的遗传疾病，其特征是易患BCC和其他肿瘤以及多种发育缺陷。NBCCS定位于染色体9q22.3，在散发性和遗传性BCC中该位点的杂合性缺失表明它起着肿瘤抑制作用。NBCCS的基因最近被克隆出来，是果蝇基因“patched”的人类同源物。果蝇的遗传学研究表明，patched是刺猬信号通路的一部分，该通路在确定发育中胚胎的多个结构中的胚胎模式和细胞命运方面很重要。人类patched在遗传性和散发性BCC中均发生突变，该基因的失活可能是BCC形成的一个必要步骤，即使不是充分步骤。对patched发挥作用的生化途径的描述可能会导致对BCC以及可能与NBCCS相关的其他肿瘤的合理药物治疗。
