MSI微衛星不穩定性
微(wei)衛(wei)(wei)(wei)(wei)(wei)星(xing)(xing)(Microsatellite,MS)是指基(ji)因組(zu)(zu)中的(de)(de)短(duan)串(chuan)聯重復(fu)序列。與(yu)正(zheng)常(chang)組(zu)(zu)織相(xiang)比(bi),腫瘤組(zu)(zu)織的(de)(de)微(wei)衛(wei)(wei)(wei)(wei)(wei)星(xing)(xing)由于重復(fu)單位的(de)(de)插(cha)入或(huo)缺失而(er)導致微(wei)衛(wei)(wei)(wei)(wei)(wei)星(xing)(xing)長度(du)(du)的(de)(de)改變,就(jiu)叫做微(wei)衛(wei)(wei)(wei)(wei)(wei)星(xing)(xing)不(bu)(bu)穩定(ding)(ding)(ding)(ding)性(xing)(xing)(Microsatellite Instability,MSI)。大量研(yan)(yan)究表明,MSI是由于錯配(pei)修復(fu)(MMR)基(ji)因發(fa)生缺陷引起的(de)(de),與(yu)腫瘤的(de)(de)發(fa)生密切(qie)相(xiang)關(guan)。約15-20%的(de)(de)結(jie)(jie)直腸(chang)癌(ai)(ai)(ai)(CRC)主要(yao)是由MSI引起。 Lynch綜合(he)征(zheng),又(you)稱遺傳(chuan)性(xing)(xing)非息肉(rou)病性(xing)(xing)結(jie)(jie)直腸(chang)癌(ai)(ai)(ai)(HNPCC),是由MMR基(ji)因胚系突變所致的(de)(de)顯(xian)性(xing)(xing)遺傳(chuan)病。研(yan)(yan)究表明,90%以上的(de)(de)Lynch綜合(he)征(zheng)具(ju)有MSI特征(zheng),而(er)在散發(fa)性(xing)(xing)結(jie)(jie)直腸(chang)癌(ai)(ai)(ai)中MSI發(fa)生率約15%。NCI建議通過檢測(ce)基(ji)因組(zu)(zu)上的(de)(de)5個(ge)單核苷酸重復(fu)的(de)(de)微(wei)衛(wei)(wei)(wei)(wei)(wei)星(xing)(xing)位點(NR-21,NR-24,BAT-25,BAT-26,MONO-27),來判(pan)斷(duan)微(wei)衛(wei)(wei)(wei)(wei)(wei)星(xing)(xing)不(bu)(bu)穩定(ding)(ding)(ding)(ding)性(xing)(xing)程度(du)(du)。與(yu)正(zheng)常(chang)組(zu)(zu)織相(xiang)比(bi),5個(ge)微(wei)衛(wei)(wei)(wei)(wei)(wei)星(xing)(xing)位點中2個(ge)或(huo)2個(ge)以上不(bu)(bu)穩定(ding)(ding)(ding)(ding)為高度(du)(du)微(wei)衛(wei)(wei)(wei)(wei)(wei)星(xing)(xing)不(bu)(bu)穩定(ding)(ding)(ding)(ding)(MSI-H),1個(ge)位點不(bu)(bu)穩定(ding)(ding)(ding)(ding)為低度(du)(du)微(wei)衛(wei)(wei)(wei)(wei)(wei)星(xing)(xing)不(bu)(bu)穩定(ding)(ding)(ding)(ding)(MSI-L),5個(ge)位點均穩定(ding)(ding)(ding)(ding)則為微(wei)衛(wei)(wei)(wei)(wei)(wei)星(xing)(xing)穩定(ding)(ding)(ding)(ding)(MSS)。研(yan)(yan)究表明,Ⅱ期MSI-H結(jie)(jie)直腸(chang)癌(ai)(ai)(ai)患者可能預(yu)后良好且(qie)無法從5-FU的(de)(de)輔(fu)助(zhu)化療中受益(yi)。臨床上已將MSI作為結(jie)(jie)直腸(chang)癌(ai)(ai)(ai)預(yu)后和制(zhi)定(ding)(ding)(ding)(ding)輔(fu)助(zhu)治療方案(an)的(de)(de)重要(yao)分子標志物,并應用于協(xie)助(zhu)Lynch綜合(he)征(zheng)篩查。