Medicine (RMH) - Research Publications

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Start date: 2011 × End date: 2013 × Subject: Cancer Genetics; Cancer and Related Disorders ×

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    Screening participation predictors for people at familial risk of colorectal cancer: a systematic review
    AIT OUAKRIM, DRISS ; LOCKETT, TREVOR ; BOUSSIOUTAS, ALEX ; Keogh, Louise ; FLANDER, LOUISA ; HOPPER, JOHN ; JENKINS, MARK ( 2013)
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    Analysis of RAD51D in Ovarian Cancer Patients and Families with a History of Ovarian or Breast Cancer
    Thompson, ER ; Rowley, SM ; Sawyer, S ; Eccles, DM ; Trainer, AH ; Mitchell, G ; James, PA ; Campbell, IG ; Ellis, NA (PUBLIC LIBRARY SCIENCE, 2013-01-25)
    Mutations in RAD51D have been associated with an increased risk of hereditary ovarian cancer and although they have been observed in the context of breast and ovarian cancer families, the association with breast cancer is unclear. The aim of this current study was to validate the reported association of RAD51D with ovarian cancer and assess for an association with breast cancer. We screened for RAD51D mutations in BRCA1/2 mutation-negative index cases from 1,060 familial breast and/or ovarian cancer families (including 741 affected by breast cancer only) and in 245 unselected ovarian cancer cases. Exons containing novel non-synonymous variants were screened in 466 controls. Two overtly deleterious RAD51D mutations were identified among the unselected ovarian cancers cases (0.82%) but none were detected among the 1,060 families. Our data provide additional evidence that RAD51D mutations are enriched among ovarian cancer patients, but are extremely rare among familial breast cancer patients.
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    A comprehensive survey of genomic alterations in gastric cancer reveals systematic patterns of molecular exclusivity and co-occurrence among distinct therapeutic targets
    Deng, N ; Goh, LK ; Wang, H ; Das, K ; Tao, J ; Tan, IB ; Zhang, S ; Lee, M ; Wu, J ; Lim, KH ; Lei, Z ; Goh, G ; Lim, Q-Y ; Tan, AL-K ; Poh, DYS ; Riahi, S ; Bell, S ; Shi, MM ; Linnartz, R ; Zhu, F ; Yeoh, KG ; Toh, HC ; Yong, WP ; Cheong, HC ; Rha, SY ; Boussioutas, A ; Grabsch, H ; Rozen, S ; Tan, P (BMJ PUBLISHING GROUP, 2012-05)
    OBJECTIVE: Gastric cancer is a major gastrointestinal malignancy for which targeted therapies are emerging as treatment options. This study sought to identify the most prevalent molecular targets in gastric cancer and to elucidate systematic patterns of exclusivity and co-occurrence among these targets, through comprehensive genomic analysis of a large panel of gastric cancers. DESIGN: Using high-resolution single nucleotide polymorphism arrays, copy number alterations were profiled in a panel of 233 gastric cancers (193 primary tumours, 40 cell lines) and 98 primary matched gastric non-malignant samples. For selected alterations, their impact on gene expression and clinical outcome were evaluated. RESULTS: 22 recurrent focal alterations (13 amplifications and nine deletions) were identified. These included both known targets (FGFR2, ERBB2) and also novel genes in gastric cancer (KLF5, GATA6). Receptor tyrosine kinase (RTK)/RAS alterations were found to be frequent in gastric cancer. This study also demonstrates, for the first time, that these alterations occur in a mutually exclusive fashion, with KRAS gene amplifications highlighting a clinically relevant but previously underappreciated gastric cancer subgroup. FGFR2-amplified gastric cancers were also shown to be sensitive to dovitinib, an orally bioavailable FGFR/VEGFR targeting agent, potentially representing a subtype-specific therapy for FGFR2-amplified gastric cancers. CONCLUSION: The study demonstrates the existence of five distinct gastric cancer patient subgroups, defined by the signature genomic alterations FGFR2 (9% of tumours), KRAS (9%), EGFR (8%), ERBB2 (7%) and MET (4%). Collectively, these subgroups suggest that at least 37% of gastric cancer patients may be potentially treatable by RTK/RAS directed therapies.