Allelotype of pancreatic adenocarcinoma using xenograft enrichment.
Allelotype of pancreatic adenocarcinoma using xenograft enrichment.
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发表时间：
1995-10
期刊：
影响因子：
11.2
通讯作者：
S. Hahn;A. Seymour;A. Hoque;M. Schutte;L. D. Costa;M. Redston;C. Caldas;Craig L. Weinstein;Aryeh Fischer;C. Yeo;R. Hruban;S. Kern
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作者：
S. Hahn;A. Seymour;A. Hoque;M. Schutte;L. D. Costa;M. Redston;C. Caldas;Craig L. Weinstein;Aryeh Fischer;C. Yeo;R. Hruban;S. Kern
已知p53和MTS 1在胰腺癌中突变失活。其他肿瘤抑制基因也可能发挥作用。为了确定可能含有额外肿瘤抑制基因的染色体臂，我们利用异种移植富集技术对胰腺癌进行了广泛的等位基因分型。88%（28/32）的原发性肿瘤产生异种移植物。18个病例用于基于PCR的等位基因型，使用283个多态性标记，超过2800个信息测定，每个病例每个染色体臂平均覆盖4.1个信息标记。在染色体1 p、9 p、17 p和18 q处观察到高度频繁的等位基因丢失（> 60%）。在3 p、6p、6 q、8 p、10 q、12 q、13 q、18 p、21 q和22 q处观察到中等频率的等位基因丢失（40-60%）。平均等位基因丢失分数为0.36。在来自12例胰腺癌的64个平行和第二次传代异种移植物中证实了等位基因和序列稳定性，确定了超过3000个单等位基因。这些发现在原发性肿瘤中得到证实。仅在两种情况下，从相应的平行异种移植物获得的等位基因丢失数据之间存在差异，可能是由于少数亚群的异种移植，反映了原发性肿瘤的遗传异质性。
p53 and MTS1 are known to be mutationally inactivated in pancreatic adenocarcinoma. Other tumor suppressor genes are likely also to play a role. To define chromosomal arms which may harbor additional tumor suppressor genes, we performed an extensive allelotype on pancreatic cancer utilizing a xenograft enrichment technique. Eighty-eight percent (28/32) of primary tumors gave rise to xenografts. Eighteen cases were used in a PCR-based allelotype using 283 polymorphic markers, over 2800 informative assays, and an average coverage of 4.1 informative markers per chromosomal arm per case. Highly frequent allelic loss (> 60%) was seen at chromosomes 1p, 9p, 17p, and 18q. Moderately frequent allelic loss (40-60%) was seen at 3p, 6p, 6q, 8p, 10q, 12q, 13q, 18p, 21q, and 22q. The average fractional allelic loss was 0.36. Allelic and sequence stability was demonstrated among 64 parallel and second-passage xenografts derived from 12 cases of pancreatic adenocarcinoma with the ascertainment of over 3000 single alleles. The findings were confirmed in primary tumors. In only two instances were discrepancies revealed between the allelic loss data obtained from corresponding parallel xenografts, probably due to the xenografting of minor subpopulations, reflecting genetic heterogeneity of the primary tumor.