Research interest
In the clinic, we only use anticancer drugs selected by clinical trials to perform best for the whole group of breast cancer patients, whereas little is known about the molecular mechanisms underlying differential drug sensitivity of breast cancer.
The focus of our group is to unravel these mechanisms in order to develop tests that may guide treatment decisions in the clinic and ultimately improve survival. For this purpose we use several genome-wide approaches and molecular techniques, in order to dissect the mechanisms that divide clinically well-defined cohorts of breast cancer patients into resistant and sensitive to a particular drug. In particular, we would like to better define the molecular subtypes of breast cancer that are sensitive to a) endocrine agents; b) bifunctional alkylating agents; c) taxanes; d) bisfosfonates; e) trastuzumab. To that end, we have initiated cell line studies, as well as retrospective and prospective clinical studies.
The NKI-AVL has excellent facilities to support these studies, including a DNA microarray facility, a surgical pathology department with a large tissue bank, an internationally recognized datacenter, an encoded patient registry for clinical research purposes, animal pathology, and a large animal facility. Since 1984, frozen tissue is available of virtually all primary breast cancers at the Dept of Pathology. Clinical follow-up data of these patients has been stored in a coded database. Most of these patients have been treated in the context of a clinical trial.
In addition, in close collaboration with the Jonkers group in our Division, we use conditional mouse models for breast cancer, and derived clonal cell lines, to study differential chemosensitivity in a controlled fashion.
Key publications
Bueno-de-Mesquita JM, van Harten WH, Retel VP, van ’t Veer LJ, van Dam FSAM, Karsenberg K, Douma KFL, van Tinteren H, Peterse JL, Wesseling J, Wu TS, Atsma D, Rutgers EJT, Brink G, Floore AN, Glas AM, Roumen RMH, Bellot FE, van Krimpen C, Rodenhuis S, van de Vijver MJ, Linn SC. (2007). Use of 70-gene signature to predict prognosis of patients with node-negative breast cancer: a prospective community-based feasibility study (RASTER). Lancet Oncol 8, 1079-1087.
Berns K, Horlings HM, Hennessy BT, Madiredjo M, Hijmans EM, Ajouaou A, Beelen K, Linn SC, Gonzalez-Angulo AM, Stemke-Hale K, Hauptmann M, Beijersbergen RL, Mills GB, van de Vijver MJ, Bernards R. (2007). A functional genetic approach identifies the PI3K pathway as a major determinant of Trastuzumab resistance in breast cancer. Cancer Cell 12, 395-402.
Linn SC, Jonkers J. (2007). Treating the genetic make-up of breast cancer: a new fashion? Expert Rev Anticancer Ther 7, 1065-67.
Meuwissen R, Linn SC, Linnoila I, Zevenhoven J, Mooi WJ, Berns A. (2003). Induction of small cell lung cancer by somatic inactivation of both Trp53 and Rb1 in a conditional mouse model. Cancer Cell 4, 181-189.
Linn SC, West RB, Pollack JP, Zhu S, Hernandez-Boussard T, Nielsen TO, Rubin BP, Patel R, Goldblum JR, Siegmund D, Botstein D, Brown PO, Gilks CB, van de Rijn M. (2003). Gene expression patterns and gene copy number changes in dermatofibrosarcoma protuberans. Am J Pathol 163, 1449-1456.
Nielsen TO, West RB, Linn SC, Alter O, Knowling MA, O'Connell JX, Zhu S, Fero M, Sherlock G, Pollack JR, Brown PO, Botstein D, van de Rijn M. (2002). Molecular characterisation of soft tissue tumours: a gene expression study. Lancet 359, 1301-1307.
Meuwissen R, Linn SC, van der Valk M, Mooi WJ, Berns A. (2001). Mouse model for lung tumorigenesis through Cre/lox controlled sporadic activation of the K-Ras oncogene. Oncogene 20, 6551-6558.
Linn SC, Pinedo HM, van Ark-Otte J, van der Valk P, Hoekman K, Honkoop AH, Vermorken JB, Giaccone G. (1997). Expression of drug resistance proteins in breast cancer, in relation to chemotherapy. Int J Cancer 71, 787-795.
Linn SC, Honkoop AH, Hoekman K, van der Valk P, Pinedo HM, Giaccone G. (1996). p53 and P-glycoprotein are often co-expressed and are associated with poor prognosis in breast cancer. Br J Cancer 74, 63-68.
Linn SC, van Kalken CK, van Tellingen O, van der Valk P, van Groeningen CJ, Kuiper CM, Pinedo HM, Giaccone G. (1994). Clinical and pharmacologic study of multidrug resistance reversal with vinblastine and bepridil. J Clin Oncol 12, 812-819.
More publications by Sabine C. Linn on Pubmed.
Biographic sketch
Sabine Linn received her medical degree (1991, cum laude) at the State University Leiden, The Netherlands, and her internal medicine board certification (2000) at the University Medical Center Utrecht, The Netherlands. She earned her PhD (1998) on the subject of multidrug resistance in solid tumors from the Free University of Amsterdam under supervision of prof. Dr H.M. Pinedo.
She was awarded a Dutch Cancer Society Research Fellowship in 2000 and developed two conditional knock-out mouse models, one for non-small cell lung cancer and one for small cell lung cancer, respectively, in close collaboration with dr Ralph Meuwissen in the laboratory of prof. dr A.J. Berns at the Netherlands Cancer Institute, Amsterdam, The Netherlands. From 2001 to 2002 she was a postdoc research fellow in the laboratories of prof. dr P.O. Brown, and prof. dr M. van de Rijn, at Stanford University Medical School, Stanford, CA, where she contributed to the development of a molecular classification for soft tissue sarcomas. Back at the Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital in Amsterdam, she earned her medical oncology certification (2002-2005) and became a senior staff member of the Division of Medical Oncology (2003).
Since 2005 she is also group leader at the Division of Molecular Biology at the Netherlands Cancer Institute where she and her research group focus on the molecular dissection of breast cancer by differential drug sensitivity. To further develop this research line Dr. Linn was awarded a Dutch Cancer Society Clinical Research Award in 2006.
Co-workers
De Bruin, Chiel PhD Post-doctoral fellow
Bueno de Mesquita, Jolien MD Graduate student
Kok, Marleen MD Graduate student
Vollebergh, Marieke MD Graduate student
Koornstra, Rutger MD Graduate student
Van der Heijden, Ingrid Technical Staff
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