Genomic change of chromosome 8 predicts the response to taxane-based neoadjuvant chemotherapy in node-positive breast cancer.
This study was performed to investigate whether the response to neoadjuvant chemotherapy in ductal-type breast cancer could be predicted by different genomic alterations. Array-based comparative genomic hybridization (aCGH) was performed on samples from 15 patients who underwent neoadjuvant chemotherapy with epirubicin plus docetaxel (ED). Frozen tissue bank samples were retrospectively selected from 8 patients who demonstrated complete pathologic response (pCR) and from 7 patients resistant to neoadjuvant chemotherapy. We performed aCGH with 4,277 human bacterial artificial chromosome (BAC) clones, scanning the genome for DNA copy number changes. In a cluster dendrogram of aCGH data, responders showed changes clustered in S940, S984, S44, S98, S130, S115, S478, and 1150T, whereas non-responder group changes clustered in S1029, S209, S219, S660, S133, S323, and S670. Compared to responders, non-responders showed more complicated genomic alterations; the most common gains were located at chromosome 8q (717%), 13q (71%), and 20q (57%), with the smallest regions of genomic gain at 8q24.3, 8q24.22, 8q24.21, 8q22.1, 8q22.2, 8q22.3, 13q21.1, 20q13.2, and 20q13.33. The most frequently deleted regions were observed on chromosome 8p (71%) and 17p (57%), with the smallest regions of deletion at 8p23.3, 8p23.2, 8p23.1, 8p21.3, 8p21.2, and 17p13.3. The results of the current study suggest that aberrations in chromosome 8 may contribute to the resistance to taxane-based neoadjuvant chemotherapy in ductal-type breast cancer. Results of our study indicate that candidate gene identification through aCGH should be validated by specific gene analysis since the sites of chromosomal aberration are quite different among studies.
Department of Surgery, Inje University Sanggye Paik Hospital, Seoul, Korea.
Sehwan
S
Han
Kyeongmee
K
Park
Eunah
E
Shin
Hyun-Jung
HJ
Kim
Jung Yeon
JY
Kim
Ji Young
JY
Kim
Geumhee
G
Gwak
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D054316:Biomarkers, Pharmacological / Q000032:analysis; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002869:Chromosome Aberrations / Q000139:chemically induced; D002898:Chromosomes, Human, Pair 8 / Q000187:drug effects* / Q000235:genetics; D055028:Comparative Genomic Hybridization / Q000379:methods; D056915:DNA Copy Number Variations; D005260:Female; D056726:Genetic Association Studies; D016678:Genome / Q000187:drug effects; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D020360:Neoadjuvant Therapy; D011379:Prognosis; D012189:Retrospective Studies; D043823:Taxoids / Q000008:administration & dosage
D054316:Biomarkers, Pharmacological; D043823:Taxoids