Loss of heterozygosity in human aberrant crypt foci (ACF), a putative precursor of colon cancer
Loss of heterozygosity in human aberrant crypt foci (ACF), a putative precursor of colon cancer
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DOI：
10.1093/carcin/bgi354
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发表时间：
2006-06-01
期刊：
影响因子：
4.7
通讯作者：
Pretlow, Theresa P.
中科院分区：
文献类型：
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作者：
Luo, Liping;Shen, Gong-Qing;Pretlow, Theresa P.
异常隐窝灶（ACF）是结肠最早的肿瘤性病变，具有遗传和表观遗传改变。大多数结肠癌中都存在抑癌基因位点杂合性丢失 (LOH)，但尚不清楚这种情况发生在肿瘤发生的早期阶段。在 32 个 ACF 和来自同一 28 名患者的正常隐窝样本中分析了接近特定基因的 9 个微卫星标记，即 APC (5q21)、PTPRJ (11p11)、p53 (17p13) 和 DCC (18q21)。在 32 个 ACF 中的 5 个中发现了 6 个杂合性丢失：4 个杂合性丢失位于 11p11，即 J 型蛋白酪氨酸磷酸酶受体 (PTPRJ) 基因和第二个独立缺失区域的位置；其他位于 5q21 和 18q21。在 32 个 ACE 中的 4 个中发现了带有单个位点标记的微卫星不稳定性 (MSI)。所有观察到的等位基因改变（LOH 和 MSI）均在 32 个 ACF 中的 8 个中发现。在腺瘤性结肠息肉病 (APC) 和 β-连环蛋白正常表达的 ACF 中发现 LOH，表明 LOH 可能在结肠瘤形成的早期就发生，甚至可能在 APC 突变之前发生。 PTPRJ 11p11 杂合性丢失中的 4 个发现中的 3 个以及 PTPRJ 的本研究中所有杂合性丢失的一半的发现表明该基因在结肠瘤形成的早期发挥作用。
Aberrant crypt foci (ACF), the earliest neoplastic lesions of the colon, have genetic and epigenetic alterations. Loss of heterozygosity (LOH) of tumor suppressor gene loci is seen in most colon cancers, but it is not known how early in tumorigenesis this takes place. Nine microsatellite markers close to specific genes, that is, APC (5q21), PTPRJ (11p11), p53 (17p13) and DCC (18q21), were analyzed in 32 ACF and samples of normal crypts from the same 28 patients. Six losses of heterozygosity were found in 5 of 32 ACF: 4 losses of heterozygosity were at 11p11, the location of the gene for protein tyrosine phosphatase receptor type J (PTPRJ) and of a second independent region of deletion; the others were at 5q21 and 18q21 Microsatellite instability (MSI) with markers for a single locus was found in 4 of 32 ACE All the observed allelic alterations (LOH and MSI) were in 8 of 32 ACF. The finding of LOH in ACF with normal expressions of adenomatous polyposis coli (APC) and beta-catenin proteins suggests that LOH can occur very early in colon neoplasia and perhaps even before APC mutations. The finding of 3 of 4 of the losses of heterozygosity at 11p11 for PTPRJ and half of all the losses of heterozygosity in this study at PTPRJ suggest that this gene plays a role early in colon neoplasia.