Intratumoral heterogeneity for amplified genes in human breast carcinoma.
Intratumoral heterogeneity was studied in human breast cancer by examining separate tumor lesions of individual patients. Tumor samples were obtained from each patient by fine-needle biopsies from 2 to 4 separate tumor lesions. We used a semi-quantitative PCR to distinguish between samples with gene amplification and single gene copy samples. Five genes were analyzed in each biopsy: MDR-1, dihydrofolate reductase, thymidylate synthase, c-erb-B2 and int-2. Three groups of patients were examined: those awaiting initiation of treatment; those receiving first-line endocrine therapy; and those receiving second-line endocrine treatment. A pattern of intratumoral heterogeneity for gene amplification was clearly apparent. The frequency of amplification was lowest before initiating therapy and highest in patients receiving second-line treatment (p = 0.023).
Lönn
U
U
Radiumhemmet, Karolinska Hospital, Stockholm, Sweden.
Lönn
S
S
Nilsson
B
B
Stenkvist
B
B
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D001706:Biopsy; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D004351:Drug Resistance; D004586:Electrophoresis; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D051518:Fibroblast Growth Factor 3; D005346:Fibroblast Growth Factors / Q000235:genetics; D005784:Gene Amplification; D014644:Genetic Variation; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011374:Progesterone / Q000627:therapeutic use; D011518:Proto-Oncogene Proteins / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases; D013629:Tamoxifen / Q000627:therapeutic use; D013739:Testosterone / Q000627:therapeutic use; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics; D013940:Thymidylate Synthase / Q000235:genetics
D004273:DNA, Neoplasm; D066246:ErbB Receptors; D051518:Fibroblast Growth Factor 3; D005346:Fibroblast Growth Factors; D011374:Progesterone; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D013629:Tamoxifen; D013739:Testosterone; D013762:Tetrahydrofolate Dehydrogenase; D013940:Thymidylate Synthase; C496444:FGF3 protein, human