Deconstructing the molecular portraits of breast cancer.
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ABSTRACT:
SUBMITTER: Prat A
PROVIDER: S-EPMC5528267 | biostudies-other | 2011 Feb
REPOSITORIES: biostudies-other
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Project description:Invasive lobular carcinoma (ILC) is the second most prevalent histologic subtype of invasive breast cancer. Here, we comprehensively profiled 817 breast tumors, including 127 ILC, 490 ductal (IDC), and 88 mixed IDC/ILC. Besides E-cadherin loss, the best known ILC genetic hallmark, we identified mutations targeting PTEN, TBX3, and FOXA1 as ILC enriched features. PTEN loss associated with increased AKT phosphorylation, which was highest in ILC among all breast cancer subtypes. Spatially clustered FOXA1 mutations correlated with increased FOXA1 expression and activity. Conversely, GATA3 mutations and high expression characterized luminal A IDC, suggesting differential modulation of ER activity in ILC and IDC. Proliferation and immune-related signatures determined three ILC transcriptional subtypes associated with survival differences. Mixed IDC/ILC cases were molecularly classified as ILC-like and IDC-like revealing no true hybrid features. This multidimensional molecular atlas sheds new light on the genetic bases of ILC and provides potential clinical options.
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Project description:Set of 65 surgical specimens of human breast tumors from 42 different individuals, using complementary DNA microarrays representing 8,102 human genes. Gene expression variation patterns within this set provided a distinctive molecular portrait of each tumor. Twenty of the tumors were sampled twice, before and after a 16-week course of doxorubicin chemotherapy, and two tumors were paired with a lymph node metastasis from the same patient. Gene expression patterns in two tumor samples from the same individual were almost always more similar to each other than either was to any other sample. This study is described more fully in Perou CM et al.(2000) Nature 406:747-52 Keywords: other
2002-06-27 | GSE61 | GEO
Project description:The risk of distant recurrence in breast cancer patients is difficult to assess with current clinical and histopathological parameters, and no validated serum biomarkers currently exist. Using a recently developed recombinant antibody microarray platform containing 135 antibodies against 65 mainly immunoregulatory proteins, we screened 240 sera from 64 patients with primary breast cancer. This unique longitudinal sample material was collected from each patient between 0 and 36 mo after the primary operation. The velocity for each serum protein was determined by comparing the samples collected at the primary operation and then 3-6 mo later. A 21-protein signature was identified, using leave-one-out cross-validation together with a backward elimination strategy in a training cohort. This signature was tested and evaluated subsequently in an independent test cohort (prevalidation). The risk of developing distant recurrence after primary operation could be assessed for each patient, using her molecular portraits. The results from this prevalidation study showed that patients could be classified into high- versus low-risk groups for developing metastatic breast cancer with a receiver operating characteristic area under the curve of 0.85. This risk assessment was not dependent on the type of adjuvant therapy received by the patients. Even more importantly, we demonstrated that this protein signature provided an added value compared with conventional clinical parameters. Consequently, we present here a candidate serum biomarker signature able to classify patients with primary breast cancer according to their risk of developing distant recurrence, with an accuracy outperforming current procedures.
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Project description:Set of 65 surgical specimens of human breast tumors from 42 different individuals, using complementary DNA microarrays representing 8,102 human genes. Gene expression variation patterns within this set provided a distinctive molecular portrait of each tumor. Twenty of the tumors were sampled twice, before and after a 16-week course of doxorubicin chemotherapy, and two tumors were paired with a lymph node metastasis from the same patient. Gene expression patterns in two tumor samples from the same individual were almost always more similar to each other than either was to any other sample. This study is described more fully in Perou CM et al.(2000) Nature 406:747-52
2002-06-27 | E-GEOD-61 | biostudies-arrayexpress
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