Hahn S A, Seymour A B, Hoque A T, Schutte M, da Costa L T, Redston M S, Caldas C, Weinstein C L, Fischer A, Yeo C J
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Cancer Res. 1995 Oct 15;55(20):4670-5.
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.
已知p53和MTS1在胰腺腺癌中发生突变失活。其他肿瘤抑制基因可能也发挥作用。为了确定可能含有其他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）的原发性肿瘤产生了异种移植物。18个病例用于基于PCR的等位基因分型，使用了283个多态性标记、超过2800次信息性检测，每个病例每个染色体臂平均有4.1个信息性标记。在染色体1p、9p、17p和18q上观察到高频等位基因缺失（>60%）。在3p、6p、6q、8p、10q、12q、13q、18p、21q和22q上观察到中等频率的等位基因缺失（40-60%）。平均等位基因缺失分数为0.36。在来自12例胰腺腺癌的64个平行和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。在原发性肿瘤中证实了这些发现。仅在两例中，从相应平行异种移植物获得的等位基因缺失数据之间存在差异，可能是由于微小亚群的异种移植，反映了原发性肿瘤的遗传异质性。
