Progress in cancer genetics: Lessons from pancreatic cancer
Progress in cancer genetics: Lessons from pancreatic cancer
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DOI：
10.1023/a:1008307913019
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发表时间：
1999-01-01
影响因子：
50.5
通讯作者：
Hruban, RH
中科院分区：
文献类型：
--
作者：
Goggins, M;Kern, SE;Hruban, RH
背景：在不远的将来，癌症分子基础的研究将有助于癌症的诊断、治疗的合理化、筛查和确定需要癌症预防策略的个体。方法：对导致胰腺癌发生的基因改变的文献进行综述。结果：几乎所有的胰腺癌都存在p16通路的失活，其中大多数失活了转化生长因子β/DPC4和p53抑癌通路。错配修复缺陷的胰腺癌具有特征性的组织学特征，可能会改善预后。最近发现的肿瘤抑制基因ALK-5、MKK4和STK11(导致Peutz-Jeghers综合征的基因)都是针对一小部分散发性胰腺癌的突变。BRCA2基因的胚系突变存在于5-10%的胰腺癌患者中。通常，这类患者没有胰腺癌家族史，被误认为是散发性疾病患者。5%到10%的胰腺癌患者有一级亲属会患上胰腺癌。一些这样的家庭也有黑色素瘤家族史，并存在生殖系p16突变。然而，导致胰腺癌遗传易感性的基因(S)仍有待于确定。结论：胰腺癌分子遗传学需要进一步的进展，以促进分子筛查试验的发展，寻找更多的家族易感基因，并为合理的治疗靶点寻找靶点。
Background: In the near future advances in the molecular basis of cancer are expected to facilitate cancer diagnosis, to rationalize treatment, to facilitate screening, and to identify individuals requiring cancer prevention strategies.Methods: The literature was reviewed concerning the genetic alterations that contribute to pancreatic cancer development.Results: Virtually all pancreatic cancers have inactivation of the p16 pathway, and the majority inactivate the TGF beta/DPC4 and p53 tumor-suppressive pathways. Pancreatic cancers with mismatch repair deficiency have a characteristic histology and may have an improved prognosis. The recently discovered tumor suppressor genes, ALK-5, MKK4, and STK11 (the gene responsible for Peutz-Jeghers syndrome) are all targeted for mutation in a small proportion of sporadic pancreatic cancers. Germline mutations of the BRCA2 gene are present in 5-10% of patients with pancreatic cancer. Typically such patients do not have a family history of pancreatic cancer and are mistaken as patients with sporadic disease. Five to 10% of patients with pancreatic cancer have first-degree relatives that will develop pancreatic cancer. Some such families also have a family history of melanoma and harbor germline p16 mutations. However, the gene(s) responsible for much of the inherited predisposition to pancreatic cancer remain to be identified.Conclusion: Further advances in pancreatic cancer molecular genetics are needed to facilitate the development of molecular screening tests, to identify additional familial susceptibility genes, and to identify targets for rational therapeutic targeting.