Partners

Complexo

Identifying the missing heritability of breast cancer via "next generation" collaboration.

Linkage analysis/positional cloning, candidate gene screening and genome-wide association study approaches have contributed to our understanding of the underlying genetic architecture of breast cancer.  Taken together, these approaches explain approximately 30% of the overall familial risk of breast cancer, implying that more, and likely rarer, genetic susceptibility alleles remain to be discovered.
The application of massively parallel sequencing has further demonstrated the complexity of human genetic variation and has raised many challenges for computational methods searching for additional breast cancer predisposition genes.  Early findings are consistent with previous indications that no single gene is likely to account for a large proportion of the remaining unexplained genetic susceptibility.  
Coordinated international collaboration offers great potential to advance the identification of additional breast cancer susceptibility genes by increasing the likelihood of identifying functionally relevant genetic variants in the same genes in multiple families. A new consortium, COMPLEXO (a name chosen to reflect the complexity of the exome), has been formed to facilitate collaborations between researchers actively applying massively parallel sequencing to understand the genetics of breast and ovarian cancer. The consortia has defined activities aimed at bringing together data and resources suitable for exome/genome sequencing initiatives and large case-control-family study resources suitable for validation of candidate breast cancer susceptibility genes in which rare mutations are associated with high to moderate risk of breast cancer. The aim of COMPLEXO is to bring to massively parallel sequencing the same power of large sample sets that have proven so successful in the consortia examining the role of common variants in cancer populations (BCAC, CIMBA, iCOGS). However, sequencing studies provide additional challenges in terms of defining specific modes of collaboration given differences in platforms, bioinformatics platforms, and the integration of ongoing studies in many centers.

Current Members

The University of Melbourne, Melbourne, Australia  |  Melissa Southey, Danny Park, Tu Nguyen-Dumont
University of Utah and Huntsman Cancer Institute, Salt Lake City, USA  |  David Goldgar, Sean Tavtigian, Bingjian Feng
Leiden University Medical Center, Netherlands  |  Peter Devilee, Florentine Hilbers
Centro Nacional de Investigaciones Oncologicas, Spain  |  Javier Benitez
Fondazione Istituto FIRC di Oncologia Molecolare and Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy  |  Paolo Radice, Paolo, Peterlongo
Peter MacCallum Cancer Centre, Melbourne, Australia  |  Ian Campbell, Ella Thompson, Alison Trainer
Queensland Institute of Medical Research, Brisbane, Australia  |  Georgia Chenevix-Trench
Mayo Clinic, Rochester, USA  |  Fergus Couch
Memorial Sloan Kettering Cancer Center, New York, USA  |  Ken Offit, Intan Schraeder
Laval University, Quebec City, Canada  |  Jacques Simard
City of Hope, Duarte California, USA  |  Susuan Neuhausen, Jefferey Weitzel
International Agency for Research on Cancer, Lyon, France  |  Fabienne Leseuer
Cancer Research Centre of Lyon, Lyon, France  |  Sylvie Mazoyer, Olga Sinilnikova, Francesca Damiola
Helsinki University Central Hospital Biomedicum Helsinki, Finland  |  Heli, Nevanlinna, Liisa Pelttari, Maral Jamshidi
University of Southern California, Los Angeles, USA  |  Susan Ramus
Syddansk Universitet, Denmark  |  Mads Thomassen
Lund University, Sweden  |   Anders Kvist, Therese Torngren
Rigshospitalet, Copenhagen, Denmark  |  Thomas Hansen
Aalborg hospital, North, Aalborg Denmark  |  Inge Pedersen, Lars Joenson

Meetings

2011
Montreal, Canada, October 14th

2012
Paris, France, January 18th
Quebec City, Canada, September 21st
San Francisco (ASHG), USA, November 6th

2013
Next meeting: El Escorial, Spain, April 24th.

For more information contact

Prof Melissa C. Southey
PhD, Grad Dip Law, FHGSA, FFSc (RCPA)
Department of Pathology
The University of Melbourne
Victoria, 3010.
Australia.
T: 61 3 8344 4895
F: 61 3 8344 4004
M: 61 438 595 395
E: msouthey@unimelb.edu.au