Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The genetic factors involved in the multistep process of carcinogenesis can be divided at least into two major categories: 1. Mutated or lost genes, which may directly represent one step in the sequential process (tumour suppressor genes); inheritance of one tumour suppressor gene causes dominant expression of the carcinogenic phenotype (the dominant inheritance is described in the accompanying paper); 2. Other genes, which lead to conditions that favour the development of cancer and generally are inherited in a recessive fashion; they are the subject of this paper. Autosomal recessively inherited diseases, such as xeroderma pigmentosum, ataxia-telangiectasia, Bloom's syndrome and Fanconi's anaemia display increased genome instability (chromosomal fragility and/or DNA-repair deficiencies) and are associated in the homozygote and probably also in the heterozygote state with defined malignancies. Neoplasms particularly of the lymphoreticular system frequently occur in patients with genetically determined immunodeficiencies (e.g. severe combined immune deficiency or Wiskott-Aldrich syndrome). People differ due to their individual genetic constitution in their responses to various classes of carcinogens such as physical and chemical agents, to dietary habits, as well as to viruses. Furthermore, tumours are often found in patients displaying premature aging (e.g. Werner's syndrome). In addition, several metabolic abnormalities such as genetic syndromes featuring chronic liver disease, but also many other inherited metabolic conditions have cancer as a regular or frequent complication.
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PMID:Recessively inherited deficiencies predisposing to cancer. 219 May 29

PALB2 [partner and localizer of BRCA2 (breast cancer early-onset 2)] [corrected] has emerged as a key player in the maintenance of genome integrity. Biallelic mutations in PALB2 cause FA (Fanconi's anaemia) subtype FA-N, a devastating inherited disorder marked by developmental abnormalities, bone marrow failure and childhood cancer susceptibility, whereas monoallelic mutations predispose to breast, ovarian and pancreatic cancer. The tumour suppressor role of PALB2 has been intimately linked to its ability to promote HR (homologous recombination)-mediated repair of DNA double-strand breaks. Because PALB2 lies at the crossroads between FA, HR and cancer susceptibility, understanding its function has become the primary focus of several studies. The present review discusses a current synthesis of the contribution of PALB2 to these pathways. We also provide a molecular description of FA- or cancer-associated PALB2 mutations.
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PMID:Exploring the roles of PALB2 at the crossroads of DNA repair and cancer. 2487 22

Abnormalities of chromosome 7 are the most common clonal chromosomal changes observed in myelodysplasia (MDS) and the second most frequent in acute myeloid leukaemia (AML) [1-5]. These changes may consist of long arm deletion (7q-) or total loss of the whole chromosome (monosomy 7) from bone marrow cells [1, 4, 6-24] and was first reported in association with myeloid disease in 1964 with the report of 3 cases of refractory anaemia, granulocytic hyperplasia [25]. The association between chromosome 7 alterations, MDS and AML in children and adults is clear, however, a rare association with lymphoid malignancies has also been recently reported. The abnormalities may occur in de novo MDS/AML, secondary cases following exposure to drugs, radiotherapy and toxins and in addition in a range of constitutional disorders including Fanconi's anaemia, congenital neutropenia and neurofibromatosis type 1 (NF1). The broad spread of conditions in which this consistent genetic change can occur leads one to speculate that there is an underlying instability in chromosome 7 and that genes on this chromosome play a role in the development of malignancy. The loss of DNA associated with malignant progression suggests the presence of a tumour suppressor gene (or genes) [26, 27]. Patients with monosomy 7 usually present as classical MDS with abnormal erythroid, megakaryocyte and myeloid differentiation [7, 28]. From a mechanistic perspective, increased cell proliferation and apoptosis is a common feature possibly induced by the failure of normal haematopoietic maturation. In all groups the presence of chromosome 7 abnormalities defines a poor prognostic group [29]. The majority of patients with MDS transform to a form of acute leukaemia resistant to therapy, including bone marrow transplantation (BMT). Although fluorescence in situ hybridization (FISH) has accelerated the study of these disorders at the cytogenetic and molecular levels, [4, 30, 31, 32, 33] no gene has been clearly implicated. A few candidate genes are under investigation. While the loss of chromsome 7 material is crutial in the malignant process it is almost certainly not the primary molecular abnormality. An initiating event genetic event predisposing to chromosome breakage and loss probably occurs in haematopoietic cells permitting chromosome 7 loss and progression to clonal malignancy as a secondary event.
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PMID:Chromosome 7 and Haematological Malignancies. 2740 2