Peltomäki P, Alfthan O, de la Chapelle A
Department of Medical Genetics, University of Helsinki, Finland.
Br J Cancer. 1991 Jun;63(6):851-8. doi: 10.1038/bjc.1991.189.
Oncogene dosage and expression were studied in 16 testicular neoplasms, 14 of germ cell and two of non-germ cell origin. In comparison with normal DNA, tumour DNA of a total of eight patients (seven with germ cell neoplasm and one with testicular lymphoma) showed increased dosages of KRAS2, PDGFA, EGFR, MET and PDGFB. The most frequent (occurring in six tumours) and prominent (up to 3-4-fold) increases were detected in the dosages of KRAS2 (on chromosome 12p) and PDGFA (chromosome 7p), relative to a reference locus from chromosome 2. Importantly, there was a similar increase in 12p dosage in general in these tumours, suggesting the presence of the characteristic isochromosome 12p marker. On the contrary, possible 7p polysomy (assessed by molecular methods) did not explain the PDGFA (or EGFR) changes in all cases. NRAS, MYCN, CSFIR, MYB, MYC, ABL, HRASI, TP53, and ERBB2 did not reveal any consistent alterations in tumour DNA. In RNA dot blot assays the expression of KRAS2, PDGFA, EGFR, or MYC was generally not increased in the tumour samples when compared to that in normal testicular tissue of the same patients although there was interindividual variation in mRNA levels. It thus appears that while oncogene dosage changes occur in a proportion of testis cancers, they are often part of changes in large chromosomal regions or whole arms and are seldom accompanied by altered expression.
对16例睾丸肿瘤进行了癌基因剂量和表达研究，其中14例起源于生殖细胞，2例起源于非生殖细胞。与正常DNA相比，总共8例患者（7例生殖细胞肿瘤患者和1例睾丸淋巴瘤患者）的肿瘤DNA显示KRAS2、PDGFA、EGFR、MET和PDGFB的剂量增加。相对于来自2号染色体的参考位点，KRAS2（位于12号染色体短臂）和PDGFA（7号染色体短臂）的剂量增加最为频繁（在6个肿瘤中出现）且显著（高达3 - 4倍）。重要的是，这些肿瘤中12号染色体短臂的剂量总体上有类似增加，提示存在特征性的12号染色体短臂等臂染色体标记。相反，可能的7号染色体多体性（通过分子方法评估）并不能解释所有病例中PDGFA（或EGFR）的变化。NRAS、MYCN、CSFIR、MYB、MYC、ABL、HRASI、TP53和ERBB2在肿瘤DNA中未发现任何一致的改变。在RNA斑点印迹分析中，与同一患者的正常睾丸组织相比，肿瘤样本中KRAS2、PDGFA、EGFR或MYC的表达通常没有增加，尽管mRNA水平存在个体差异。因此，虽然一部分睾丸癌中发生了癌基因剂量变化，但它们通常是大染色体区域或整条染色体臂变化的一部分，很少伴有表达改变。
