title: Genomic alterations in primary breast cancers compared with their sentinel and more distal lymph node metastases: an aCGH study.
abstract: Metastatic potential of breast cancer may be associated with specific genomic alterations and the earliest metastases are likely to be found in the sentinel lymph nodes (SLN). Using array comparative genomic hybridization (aCGH), we compared the genomes of primary breast invasive duct carcinomas (IDCs), their sentinel and more distal lymph node metastases, and IDCs without nodal metastasis. Thirty-three samples from 22 patients with IDC were subjected to aCGH: 8 IDC samples from patients without lymph node metastasis, 11 IDCs associated with SLN metastases out of which 7 had paired samples of metastases, and 14 samples of lymph node metastases out of which 8 were sentinel-distal pairs from 4 patients. aCGH data were analyzed by correlation of genomic profiles, cluster analysis, segmentation, and peak identification. Quantitative real-time PCR was used for data validation. We observed high genomic similarity between primary tumors and their nodal metastases as well as between metastases to the sentinel and distal lymph nodes. Several recurrent alterations were detected preferentially in IDC associated with SLN metastases compared to IDCs without metastasis. Amplification within the 17q24.1-24.2(59.96-62.76 Mb) region was associated with presence of sentinel or distal lymph node metastases; larger tumor size and higher histological grade. In our samples, there were genomic events associated with metastatic progression, which could be detected in both primary tumors and LN metastases. Gain on 17q24.1-24.2 is a candidate region for further testing as a predictor of nodal metastasis.
authors.affiliation: Division of Applied Medical Oncology, Ontario Cancer Institute/Princess Margaret Hospital, Toronto, ON, Canada.
authors.forename: Chunjie
authors.initials: C
authors.lastname: Wang
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Iakovlev
authors.forename: Vietty
authors.initials: V
authors.lastname: Wong
authors.forename: Stephanie
authors.initials: S
authors.lastname: Leung
authors.forename: Keisha
authors.initials: K
authors.lastname: Warren
authors.forename: Gaiane
authors.initials: G
authors.lastname: Iakovleva
authors.forename: Nona C R
authors.initials: NC
authors.lastname: Arneson
authors.forename: Melania
authors.initials: M
authors.lastname: Pintilie
authors.forename: Naomi
authors.initials: N
authors.lastname: Miller
authors.forename: Bruce
authors.initials: B
authors.lastname: Youngson
authors.forename: David R
authors.initials: DR
authors.lastname: McCready
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Done
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000556:secondary; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D005260:Female; D015894:Genome, Human; D006801:Humans; D007124:Immunoenzyme Techniques; D008198:Lymph Nodes; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011379:Prognosis; D021701:Sentinel Lymph Node Biopsy