Yokota T, Matsumoto S, Yoshimoto M, Kasumi F, Akiyama F, Sakamoto G, Nakamura Y, Emi M
Department of Molecular Biology, Nippon Medical School, Kawasaki.
Jpn J Cancer Res. 1997 Oct;88(10):959-64. doi: 10.1111/j.1349-7006.1997.tb00315.x.
DPC4 and DCC, putative tumor suppressor genes implicated in the genesis of several types of human cancer, lie on the long arm of human chromosome 18. We examined 200 primary breast cancers for allelic losses on chromosome 18, using 15 microsatellite markers distributed along the long arm. Allelic loss was detected most frequently (29-30%) at loci mapped to 18q21. Deletion mapping of the 34 tumors showing partial or interstitial deletions identified a commonly deleted region within the 4-cM interval flanked by D18S474 and D18S487 at 18q21.1-q21.3. Although this interval included the DPC4 and DCC genes, we excluded DPC4 from candidacy when polymerase chain reaction-single-strand conformation polymorphism analysis of each exon failed to detect abnormalities in any of the 54 breast cancers that exhibited loss of heterozygosity involving 18q. Allelic loss on 18q was found more frequently in tumors of the solid tubular histological type (24 of 55, 44%) than in other types (24 of 113, 21%) (P = 0.0049). The results suggest that a tumor suppressor gene located within the 4-cM region at 18q21, either DCC or another gene not yet identified, may play a role in the development of some sporadic breast cancers, particularly those of the solid tubular type.
DPC4和DCC这两个被认为与多种人类癌症发生相关的潜在抑癌基因，位于人类18号染色体长臂上。我们使用沿着长臂分布的15个微卫星标记，检测了200例原发性乳腺癌中18号染色体上的等位基因缺失情况。在定位到18q21的位点上，等位基因缺失的检测频率最高（29%-30%）。对34例显示部分或中间缺失的肿瘤进行缺失图谱分析，确定了在18q21.1-q21.3区域内，由D18S474和D18S487侧翼的4厘摩区间内的一个常见缺失区域。尽管这个区间包括DPC4和DCC基因，但当对每个外显子进行聚合酶链反应-单链构象多态性分析，未能在54例显示涉及18q杂合性缺失的乳腺癌中检测到任何异常时，我们将DPC4排除在候选基因之外。18q上的等位基因缺失在实性管状组织学类型的肿瘤中（55例中的24例，44%）比在其他类型中（113例中的24例，21%）更频繁地被发现（P = 0.0049）。结果表明，位于18q21 4厘摩区域内的一个抑癌基因，要么是DCC，要么是另一个尚未确定的基因，可能在一些散发性乳腺癌的发生中起作用，特别是那些实性管状类型的乳腺癌。
