Adenoid cystic carcinomas constitute a genomically distinct subgroup of triple-negative and basal-like breast cancers.
Adenoid cystic carcinoma (AdCC) is a rare form of triple-negative and basal-like breast cancer that has an indolent clinical behaviour. Four breast AdCCs were recently shown to harbour the recurrent chromosomal translocation t(6;9)(q22-23;p23-24), which leads to the formation of the MYB-NFIB fusion gene. Our aims were (i) to determine the prevalence of the MYB-NFIB fusion gene in AdCCs of the breast; (ii) to characterize the gene copy number aberrations found in AdCCs; and (iii) to determine whether AdCCs are genomically distinct from histological grade-matched or triple-negative and basal-like invasive ductal carcinomas of no special type (IDC-NSTs). The presence of the MYB-NFIB fusion gene was investigated in 13 AdCCs of the breast by fluorescence in situ hybridization (FISH) and reverse transcriptase-PCR (RT-PCR), and MYB and BRCA1 RNA expression was determined by quantitative RT-PCR. Fourteen AdCCs, 14 histological grade-matched IDC-NSTs, and 14 IDC-NSTs of triple-negative and basal-like phenotype were microdissected and subjected to high-resolution microarray-based comparative genomic hybridization (aCGH). The MYB-NFIB fusion gene was detected in all but one AdCC. aCGH analysis demonstrated a relatively low number of copy number aberrations and a lack of recurrent amplifications in breast AdCCs. Contrary to grade-matched IDC-NSTs, AdCCs lacked 1q gains and 16q losses, and in contrast with basal-like IDC-NSTs, AdCCs displayed fewer gene copy number aberrations and expressed MYB and BRCA1 at significantly higher levels. Breast AdCCs constitute an entity distinct from grade-matched and triple-negative and basal-like IDC-NSTs, emphasizing the importance of histological subtyping of triple-negative and basal-like breast carcinomas.
The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, UK.
Daniel
D
Wetterskog
Maria Angeles
MA
Lopez-Garcia
Maryou B
MB
Lambros
Roger
R
A'Hern
Felipe C
FC
Geyer
Fernanda
F
Milanezi
Maria C
MC
Cabral
Rachael
R
Natrajan
Arnaud
A
Gauthier
Kai-Keen
KK
Shiu
Nicholas
N
Orr
Sami
S
Shousha
Zoran
Z
Gatalica
Alan
A
Mackay
Jose
J
Palacios
Jorge S
JS
Reis-Filho
Britta
B
Weigelt
D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D003528:Carcinoma, Adenoid Cystic / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000473:pathology; D005260:Female; D018628:Gene Dosage; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D042282:Microdissection; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D020893:Receptor, ErbB-3 / Q000096:biosynthesis / Q000235:genetics; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000235:genetics; D011980:Receptors, Progesterone / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis
C545202:MYB-NFIB fusion protein, human; D015514:Oncogene Proteins, Fusion; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D020893:Receptor, ErbB-3