Data from: Clonal relatedness between lobular carcinoma in situ and synchronous malignant lesions

INTRODUCTION: Lobular carcinoma in situ (LCIS) has been accepted as a
marker of risk for the development of invasive breast cancer, yet modern
models of breast carcinogenesis include LCIS as a precursor of low-grade
carcinomas. We provide evidence favoring a clonal origin for LCIS and
synchronous estrogen receptor-positive malignant lesions of the ductal and
lobular phenotype. METHODS: Patients with prior LCIS undergoing mastectomy
were identified preoperatively from 2003-2008. Specimens were widely
sampled, and frozen blocks were screened for LCIS and co-existing
malignant lesions, and subject to microdissection. Samples from 65
patients were hybridized to the Affymetrix SNP 6.0 array platform. Cases
with both an LCIS sample and an associated ductal carcinoma in situ (DCIS)
or invasive tumor sample were evaluated for patterns of somatic copy
number changes to assess evidence of clonal relatedness. RESULTS: LCIS was
identified in 44 of the cases, and among these, a DCIS and/or invasive
lesion was also identified in 21 cases. A total of 17 tumor pairs had
adequate DNA/array data for analysis, including 9 pairs of LCIS/invasive
lobular cancer (ILC), 4 pairs of LCIS/DCIS, and 4 LCIS/invasive ductal
cancer (IDC). Overall, 7 pairs (41%) were judged to be clonally related;
in 5 (29%), evidence suggested clonality but was equivocal, and 5 (29%)
were considered independent. Clonal pairs were observed with all matched
lesion types and low and high histological grades. We also show anecdotal
evidence of clonality between a patient-matched triplet of LCIS, DCIS, and
IDC. CONCLUSIONS: Our results support the role of LCIS as a precursor in
the development of both high- and low-grade ductal and lobular cancers.