本文研究中，研究者對(duì)3000名病人的血液樣本進(jìn)行分析研究者Li Ding說道，我們并不知道有多少70歲以上的個(gè)體都攜帶有這些風(fēng)險(xiǎn)突變，這項(xiàng)研究的重點(diǎn)就在于對(duì)大量個(gè)體進(jìn)行了篩查，研究者并不知道是否其中的一個(gè)突變會(huì)引發(fā)個(gè)體更高的血癌風(fēng)險(xiǎn)，而后續(xù)還需要進(jìn)行更多的研究來揭示患血癌的風(fēng)險(xiǎn)。
接下來的研究中，研究人員主要對(duì)556個(gè)已知的癌癥基因進(jìn)行分析，在341名40至49歲的患者中，低于1%的患者攜帶19個(gè)和白血病或淋巴瘤相關(guān)的基因；但是在475名70歲至79歲的個(gè)體中，有超過5%的個(gè)體攜帶有上述的19個(gè)風(fēng)險(xiǎn)基因，而在132名80歲至89歲的個(gè)體中有超過6%的個(gè)體中都存在上述基因突變。
研究者指出，19個(gè)風(fēng)險(xiǎn)基因中有9個(gè)基因會(huì)重復(fù)突變，這也是誘發(fā)突變的血細(xì)胞不斷增殖的原因。當(dāng)前的研究似乎低估了攜帶白血病和淋巴瘤風(fēng)險(xiǎn)基因的患者的百分比，因?yàn)檠芯咳藛T僅僅鑒別出了很小的一部分突變，并沒有鑒別出機(jī)體遺傳物質(zhì)的較大范圍的結(jié)構(gòu)性突變或插入突變等。因此對(duì)于人類來講，進(jìn)行遺傳測(cè)試檢測(cè)是否攜帶和白血病及淋巴瘤相關(guān)的基因突變來作為預(yù)測(cè)血癌風(fēng)險(xiǎn)還為時(shí)過早。
最后研究者Timothy Ley博士表示，我們并不想讓每一個(gè)人都認(rèn)為他們必須進(jìn)行篩查來檢測(cè)其患癌的風(fēng)險(xiǎn)，理解增加個(gè)體患血癌風(fēng)險(xiǎn)的基因突變的機(jī)制或許還需要很長(zhǎng)一段路要走，而此時(shí)進(jìn)行遺傳測(cè)試或許對(duì)于個(gè)體并無益處。如果研究人員可以在千百萬人中重復(fù)上述的實(shí)驗(yàn)結(jié)果，那么他們就可以更加準(zhǔn)確地鑒別出個(gè)體患白血病及淋巴癌的風(fēng)險(xiǎn)了。
轉(zhuǎn)化醫(yī)學(xué)網(wǎng)推薦的原文摘要：
Age-related mutations associated with clonal hematopoietic expansion and malignancies
Nature Medicine doi:10.1038/nm.3733
Mingchao Xie, Charles Lu, Jiayin Wang, Michael D McLellan, Kimberly J Johnson, Michael C Wendl, Joshua F McMichael, Heather K Schmidt, Venkata Yellapantula, Christopher A Miller, Bradley A Ozenberger, John S Welch, Daniel C Link, Matthew J Walter, Elaine R Mardis, John F Dipersio, Feng Chen, Richard K Wilson, Timothy J Ley & Li Ding
Several genetic alterations characteristic of leukemia and lymphoma have been detected in the blood of individuals without apparent hematological malignancies. The Cancer Genome Atlas (TCGA) provides a unique resource for comprehensive discovery of mutations and genes in blood that may contribute to the clonal expansion of hematopoietic stem/progenitor cells. Here, we analyzed blood-derived sequence data from 2,728 individuals from TCGA and discovered 77 blood-specific mutations in cancer-associated genes, the majority being associated with advanced age. Remarkably, 83% of these mutations were from 19 leukemia and/or lymphoma-associated genes, and nine were recurrently mutated (DNMT3A, TET2, JAK2, ASXL1, TP53, GNAS, PPM1D, BCORL1 and SF3B1). We identified 14 additional mutations in a very small fraction of blood cells, possibly representing the earliest stages of clonal expansion in hematopoietic stem cells. Comparison of these findings to mutations in hematological malignancies identified several recurrently mutated genes that may be disease initiators. Our analyses show that the blood cells of more than 2% of individuals (5–6% of people older than 70 years) contain mutations that may represent premalignant events that cause clonal hematopoietic expansion.
