Need Help?

33 patients with Monoclonal Gammopathy of Undetermined Significance (MGUS)

Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant precursor of multiple myeloma (MM) with a 1% risk of progression per year. Although targeted analyses have shown the presence of specific genetic abnormalities such as IGH translocations, RB1 deletion, 1q gain, hyperdiploidy or RAS genes mutations, little is known about molecular mechanism of malignant transformation. We have performed whole exome sequencing together with SNP array analysis in 33 flow-cytometry separated abnormal PC samples of MGUS patients to describe somatic gene mutations and chromosome changes at the genome-wide level. Non-synonymous mutations (NS-SNVs) and copy number alterations (CNAs) were present in 97.0% and in 63.6% of cases, respectively. Importantly, the number of somatic mutations was significantly lower in MGUS compared to MM (p<10-4) and we have identified 6 myeloma significantly mutated genes which are KRAS, NRAS, DIS3, HIST1H1E, EGR1 and LTB in the MGUS dataset. We also found a positive correlation with increasing chromosome changes and somatic mutations. IGH translocations were present in 27.3% of cases comprising t(4;14), t(11;14), t(14;16) or t(14;20) and were in a similar frequency to MM, which corresponded with primary lesion hypothesis. Data from this study showed MGUS is a genetically comprehensive disease, however overall genetic instability is significantly lower compared to MM.

Request Access

Human Genetic Data Access Agreement between the Institute of Cancer Research and other parties for access to the Amyloidosis exome sequencing dataset.

HUMAN GENETIC DATA ACCESS AGREEMENT FOR INSTITUTIONS (“Agreement”)Between:(1) The Institute of Cancer Research: Royal Cancer Hospital of 123 Old Brompton Road, London SW7 3RP, UK (“ICR”); and(2) [INSERT INSTITUTION DETAILS] (the “Recipient”.)In response to the Recipient's request for access to the Data (as set out in Appendix A), ICR and the Recipient agree as follows:1Definitions1.1“NCRI Myeloma XI Exome Sequencing Dataset” (“My11_Exome”) shall mean the project undertaken at The Institute of Cancer Research, UK to identify genetic sequence variants and mutations relevant to the development of multiple myeloma;1.2 “Data” shall mean all and any human genetic data obtained from the My11_Exome including any additional annotations such as age, sex, molecular subgroup. Explicitly, Data does not include samples or biological materials;1.3 “Data Subject” shall mean the person (irrespective of state of health) to whom Data refers and who has been informed of the purpose for which the Data is held and has given his/her informed consent thereto;1.4 “Intellectual Property” means (i) patents, designs, trade marks and trade names (whether registered or unregistered), copyright and related rights, database rights, know-how and confidential information; (ii) all other intellectual property rights and similar or equivalent rights anywhere in the world which currently exist or are recognised in the future; and (iii) applications, extensions and renewals in relation to any such rights;1.5 “Registered User” shall mean a Researcher (or an individual conducting Research under the direct supervision of that Researcher) that is employed by the Recipient and is bound by confidentiality and non-use obligations in respect of Data and who has signed this Agreement and has received acknowledgement of its acceptance. For the avoidance of doubt, “Registered User” may also include students of the Recipient, visiting academics, contractors, sub-contractors or independent consultants provided that any such individual is bound by confidentiality and non-use obligations no less onerous then those binding the Recipient’s employees;1.6 “Research” shall mean non-commercial research undertaken by the Recipient that seeks to advance the understanding and treatment of cancer and closely related diseases, and work on statistical methods that may be applied to such Research as set out in Appendix A;1.7“Researcher(s)” shall mean an individual or individuals carrying out Research who:(a) in the case of an individual seeking access to Data held solely under the control of ICR, has authored a relevant peer-reviewed article that ICR can locate on PubMed and who is still working in the field; or(b) in the case of an individual seeking access to Data held as part of a wider consortium, is a successful applicant to the consortium data access committee.2Purpose2.1The Recipient agrees to use Data only for the purposes of the Research described in Appendix A.3 Confidentiality3.1 The Recipient agrees to preserve, at all times, the confidentiality of Data pertaining to identifiable Data Subjects. In particular, the Recipient undertakes not to use, or attempt to use the Data to deliberately compromise or otherwise infringe the confidentiality of information on Data Subjects and their right to privacy. Recipient or Registered Users will not use Data either alone or in conjunction with any other information in any effort whatsoever to establish the individual identities of any Data Subject from whom Data were obtained.4 Data Protection4.1 The Recipient agrees that it, and its Registered Users, are covered by and shall comply with the obligations contained in the Data Protection Act 1998 as amended from time to time, or equivalent national provisions no less onerous then those contained in the Data Protection Act. In particular, the Recipient shall be responsible for ensuring that Registered Users understand and will comply with their duties under such legislation in relation to the handling, storage and use of Data and the rights of Data Subjects.4.2 The Recipient agrees that it, and its Registered Users, shall not analyse or make any use of the Data in such a way that has the potential to:(a) lead to the identification of any Data Subject; or(b) compromise the anonymity of any Data Subject in any way.5 Access and Governance5.1 The Recipient agrees that it shall take all reasonable security precautions to keep the Data confidential, such precautions to be no less onerous than those applied in respect of the Recipient’s own confidential information.5.2 The Recipient agrees to only give access to Data, in whole or part, or any material derived from the Data, to a Registered User. The Recipient agrees that before it gives any Registered User access to Data, it shall first show the Registered User a copy of this Agreement and shall inform the Registered User that he or she must comply with the obligations contained in this Agreement and sign up to the provisions of this Agreement in the form set out at the end of this Agreement. The Recipient shall provide ICR with a copy of the Registered User’s acceptance form within thirty (30) days of the date of acceptance by the Registered User.5.3 The Recipient agrees that it shall only give Registered Users that are not Researchers (including but not limited to students or new researchers to the field) access to the Data if they are supervised by a Researcher who will take responsibility for such Registered Users’ use of the Data.5.4 The Recipient shall take responsibility for all Researchers and Registered Users who have access to the Data. Recipient will procure that such Researchers and/or Registered Users shall be bound by the terms and conditions of access set out in this Agreement.5.5 ICR reserves the right to request and inspect data security and management documentation to ensure the adequacy of data protection measures in countries that have no national laws comparable to that pertaining in the European Economic Area (EEA).6Errors6.1The Recipient agrees to notify the ICR of any errors detected in the Data.7Data reissue7.1 The Recipient accepts that Data will be reissued from time to time, with suitable versioning. If Data is reissued at the request of sample donors and/or as the result of other ethical scrutiny, the Recipient agrees to destroy all earlier versions of the Data.8Intellectual Property8.1The Recipient recognises that nothing in this Agreement shall operate to transfer to the Recipient or its Registered Users any Intellectual Property rights in or relating to the Data.8.2The Data shall at all times remain the property of ICR or of ICR’s designated assignee. Recipient shall retain title to any Intellectual Property made through the Recipient’s use of the Data, except to the extent such Intellectual property incorporates the Data.8.3 The Recipient and its Registered Users shall have the right to develop Intellectual Property based on comparisons with their own data.9Publications9.1 The Recipient agrees to acknowledge in any work based in whole or part on the Data, the published paper from which the Data derives, the version of the Data, and the role of the ICR and its funders in its distribution. The Recipient agrees to use the acknowledgement wording provided for the relevant Data in its publication. The Recipient will also declare in any such work that those who carried out the original analysis and collection of the Data bear no responsibility for the further analysis or interpretation of it by the Recipient.10Termination of Agreement10.1 This Agreement will terminate immediately upon any breach of the provisions of this Agreement by the Recipient or by the Recipient’s Registered Users.10.2The Recipient accepts that the changing ethical framework of human genetic research may lead to: (i) alteration to the provisions of this Agreement, in which case the Recipient may accept such alterations or terminate this Agreement; or (ii) the withdrawal of this Agreement in extreme circumstances.10.3 Either party shall have the right to terminate this Agreement with immediate effect upon giving written notice of termination to the other party.10.4 In the event that this Agreement is terminated in accordance with this Clause 10 the Recipient shall return or destroy all Data at the direction of ICR.11Costs11.1 The Recipient acknowledges that ICR shall incur costs in providing the Data to the Recipient, including but not limited to administrative costs and the cost of obtaining appropriate data storage devices. The Recipient agrees to pay, on the request of ICR, such reasonable costs as ICR may incur in providing the Data, within thirty (30) days of ICR making such a request for payment.12 Legal statement12.1The Recipient acknowledges that ICR and all other parties involved in the creation, funding or protection of the Data:(a) make no warranty or representation, express or implied as to the accuracy, quality or comprehensiveness of the Data; and(b) exclude to the fullest extent permitted by law all liability for actions, claims, proceedings, demands, losses (including but not limited to loss of profit), costs, awards damages and payments made by the Recipient that may arise (whether directly or indirectly) in any way whatsoever from the Recipient’s use of the Data, or from the unavailability of, or break in access to the Data for whatever reason.12.2Subject to clause 12.3, the Recipient shall hold harmless and indemnify ICR, its employees, agents and directors for all liabilities, demands, damages, expenses and losses (the “Losses”) arising directly or indirectly out of the Recipient's use of the Data, except to the extent the Losses are due to ICR’s negligence.12.3Under no circumstances shall either party be liable to the other, whether in contract, tort (including negligence or breach of statutory duty) or otherwise howsoever arising for any loss of profit, business, reputation, contracts or anticipated savings or any other indirect, special or consequential losses which arise, directly or indirectly, from any default on the part of the other party. Nothing in this Agreement is intended to limit or exclude any liability for fraud.12.4 The Recipient understands that all the Data is protected by copyright and other intellectual property rights, such that duplication or sale of all of or part of the Data on any media is not permitted under any circumstances, except with the prior written consent of ICR.12.5 The Recipient accepts that it may be necessary for ICR to alter the terms of this Agreement from time to time in order to address new concerns. In this event, ICR will contact Recipient to inform Recipient of any changes and Recipient agrees that its continued use of the Data shall be dependent on the parties entering into a new version of the Agreement.13 Governing Law13.1 This Agreement (and any dispute, controversy, proceedings or claim of whatever nature arising out of this Agreement or its formation) shall be construed, interpreted and governed by English Law and shall be subject to the exclusive jurisdiction of the courts of England and Wales. Nothing in this clause shall however prevent either party from seeking interim relief in any court of competent jurisdiction.AGREED by the parties through their authorised signatoriesINSTITUTE OF CANCER RESEARCH: ROYAL CANCER HOSPITALAuthorised Signature:Name:Title:Date:RECIPIENT: [RECIPIENT NAME]Authorised Signature: Name: Title: Address: Telephone No: Email: Registered Users:The Registered Users acknowledge the contents of this Agreement and agree to comply with the obligations herein. For the avoidance of doubt the Registered Users are not a party to this Agreement.Signature:Name:Title:Date:Email:Signature:Name:Title:Date:Email:Please send completed forms to:Professor Gareth MorganThe Institute of Cancer Research15 Cotswold RoadSutton, SM2 5NGUnited KingdomICR complies with the requirements of the Data Protection Act 1998 with regard to the collection, storage, processing and disclosure of personal information and is committed to upholding the Act's core Data Protection Principles. Information collected under the Agreement will be used for the purposes of maintaining the Agreement, and may be used for statistical reporting. Appendix AAPPLICATION FOR ACCESS TO GENOTYPE DATAApplications for access to data can be submitted at any time. The ICR MY11_Exome Data Access Committee will consider applications and provide a decision within 1 month of receipt.Name of applicant and co-applicant(s), including affiliations and contact details.Enter the Primary E-mail correspondence E-mail address you would like to usePlease ensure that a full postal and email address is included for each applicant.PhD student and Post-doctoral fellow applicants must include their Supervisor / Principal Investigator as a co-applicant and provide their full contact details.Title of Project (in less than 30 words).Genotype Data requested Research QuestionPlease provide a clear description of the project and its specific aims in no more than 750 words. This should include specific details of what you plan to do with the data and include key references. FeasibilityPlease describe fully your experience and expertise, and that of your collaborators, and how this will be applied to the proposed study. A publication list MUST be provided for the applicant, co-applicants and PhD supervisors where PhD students have applied. The committee needs assurance of competence in handling datasets of this size and nature.

Studies are experimental investigations of a particular phenomenon, e.g., case-control studies on a particular trait or cancer research projects reporting matching cancer normal genomes from patients.

Study ID Study Title Study Type
EGAS00001001658 Other

This table displays only public information pertaining to the files in the dataset. If you wish to access this dataset, please submit a request. If you already have access to these data files, please consult the download documentation.

ID File Type Size Located in
EGAF00001174857 bam 8.0 GB
EGAF00001174858 bam 9.6 GB
EGAF00001174859 bam 7.6 GB
EGAF00001174860 bam 10.2 GB
EGAF00001174861 bam 7.8 GB
EGAF00001174862 bam 13.7 GB
EGAF00001174863 bam 7.5 GB
EGAF00001174864 bam 9.8 GB
EGAF00001174865 bam 7.8 GB
EGAF00001174866 bam 10.4 GB
EGAF00001174867 bam 7.3 GB
EGAF00001174868 bam 10.3 GB
EGAF00001174869 bam 7.9 GB
EGAF00001174870 bam 10.2 GB
EGAF00001174871 bam 10.1 GB
EGAF00001174872 bam 9.9 GB
EGAF00001174873 bam 8.8 GB
EGAF00001174874 bam 9.5 GB
EGAF00001174875 bam 7.3 GB
EGAF00001174876 bam 10.4 GB
EGAF00001174877 bam 9.1 GB
EGAF00001174878 bam 9.9 GB
EGAF00001174879 bam 10.6 GB
EGAF00001174880 bam 9.5 GB
EGAF00001174881 bam 10.4 GB
EGAF00001174882 bam 10.5 GB
EGAF00001174883 bam 9.1 GB
EGAF00001174884 bam 9.1 GB
EGAF00001174885 bam 9.5 GB
EGAF00001174886 bam 10.3 GB
EGAF00001174887 bam 9.7 GB
EGAF00001174888 bam 10.2 GB
EGAF00001174889 bam 9.9 GB
EGAF00001174890 bam 9.1 GB
EGAF00001174891 bam 11.2 GB
EGAF00001174892 bam 12.5 GB
EGAF00001174893 bam 10.2 GB
EGAF00001174894 bam 8.4 GB
EGAF00001174895 bam 11.0 GB
EGAF00001174896 bam 10.5 GB
EGAF00001174897 bam 11.4 GB
EGAF00001174898 bam 9.3 GB
EGAF00001174899 bam 12.3 GB
EGAF00001174900 bam 10.1 GB
EGAF00001174901 bam 10.6 GB
EGAF00001174902 bam 8.5 GB
EGAF00001174903 bam 9.9 GB
EGAF00001174904 bam 10.1 GB
EGAF00001174905 bam 9.4 GB
EGAF00001174906 bam 10.1 GB
EGAF00001174907 bam 10.0 GB
EGAF00001174908 bam 9.7 GB
EGAF00001174909 bam 11.0 GB
EGAF00001174910 bam 10.5 GB
EGAF00001174911 bam 11.1 GB
EGAF00001174912 bam 9.1 GB
EGAF00001174913 bam 10.2 GB
EGAF00001174914 bam 10.5 GB
EGAF00001174915 bam 10.3 GB
EGAF00001174916 bam 9.8 GB
EGAF00001174917 bam 10.2 GB
EGAF00001174918 bam 9.6 GB
EGAF00001174919 bam 10.6 GB
EGAF00001174920 bam 9.1 GB
EGAF00001174921 bam 9.6 GB
EGAF00001174922 bam 10.6 GB
66 Files (648.6 GB)