Skip to main content

COVID-19 Resources

What people with cancer should know: https://www.cancer.gov/coronavirus

Guidance for cancer researchers: https://www.cancer.gov/coronavirus-researchers

Get the latest public health information from CDC: https://www.cdc.gov/coronavirus

Get the latest research information from NIH: https://www.covid19.nih.gov

Grant Details

Grant Number: 5R01CA137365-05 Interpret this number
Primary Investigator: Qureshi, Abrar
Organization: Brigham And Women'S Hospital
Project Title: Molecular Signatures of Melanoma Histology and Progression: a Population Based a
Fiscal Year: 2013


Abstract

DESCRIPTION (provided by applicant): critical obstacle to molecular and genomic classification of primary melanoma has been the requirement to provide prognostic measures (i.e. Breslow thickness) and related histologic parameters in formalin-fixed, paraffin-embedded (FFPE) biospecimens, where unlike frozen material, unadulterated mRNA and DNA have been difficult or impossible to extract and study. With our collaborators, we have successfully applied a novel technology first developed by Fan et al in 2004 for global gene expression profiling of melanoma FFPE biospecimens. This platform, designated DASL for DNA-mediated Annealing, Selection, extension, and Ligation) renders formalin-fixed biospecimens embedded and archived in the form of paraffin blocks usable for gene expression analysis. We found two distinct subclasses characterized by two robust signatures: one broadly defined by a cluster of microphthalmia and melanocyte differentiation genes ("MITF" class) and a more heterogeneous group of inflammation, innate immune, and growth-related genes ("IIG" class). Our preliminary data indicate that DASL can successfully profile and recover the 2-class structure from FFPE primary melanomas in the Nurses Health Study 1. The Channing Laboratory at Brigham and Women's Hospital is home to large cohort studies, i.e. the Nurses' Health Study 1 (NHS1), Nurses' Health Study-2 (NHS2) and the Health Professionals Follow-up Study (HPFS). The further strength of these cohorts lies in disease follow-up with bi-annual updates on new cases and mortality and availability of tissue blocks from the primary tumor site for melanoma cases in the cohorts. We hypothesize that melanoma aggressiveness is determined by MITF/IIG classes and we propose to evaluate whether this 2-class structure is associated with known histological parameters (e.g. Breslow thickness), and melanoma recurrence/mortality. With access to unique population-based national cohorts and development of new technologies with our collaborators, the specific aims of this proposal are as follows: Specific Aim 1: Develop molecular signatures of NHS, NHS2 and HPFS melanoma FFPE samples using an Illumina expression array platform with over 6000 genes and a Sequonome platform to sequence MC1R and genotype specific loci for BRAF and NRAS to: a. Assign MITF or IIG class for each melanoma sample and evaluate their association with BRAF/NRAS/MC1R status and determinants of melanoma histology (e.g. Breslow thickness, Clark's level, vertical growth phase) b. Evaluate genome-wide (6,000 genes) class discovery for each melanoma sample and evaluate their association with BRAF/ NRAS/MC1R status and determinants of melanoma histology (e.g. Breslow, Clark's level, vertical growth phase) Specific Aim 2: Using the transcriptional and genomic signatures from Aim 1 to: a. Assign MITF or IIG class association with BRAF/NRAS/MC1R status and melanoma recurrence and mortality due to melanoma b. Evaluate genome-wide (6,000 genes) association with BRAF/NRAS/MC1R status and melanoma recurrence and mortality due to melanoma



Publications

Niacin intake and risk of skin cancer in US women and men.
Authors: Park S.M. , Li T. , Wu S. , Li W.Q. , Weinstock M. , Qureshi A.A. , Cho E. .
Source: International journal of cancer, 2017-05-01; 140(9), p. 2023-2031.
EPub date: 2017-02-14.
PMID: 28152570
Related Citations

Risk of second primary cancer associated with pre-diagnostic smoking, alcohol, and obesity in women with keratinocyte carcinoma.
Authors: Park S.M. , Li T. , Wu S. , Li W.Q. , Qureshi A.A. , Stampfer M. , Cho E. .
Source: Cancer epidemiology, 2017 04; 47, p. 106-113.
EPub date: 2017-02-24.
PMID: 28242577
Related Citations

Type 2 diabetes mellitus and risk of cutaneous squamous cell carcinoma.
Authors: Chen S.T. , Li T. , Han J. , Qureshi A.A. , Cho E. .
Source: Journal of the American Academy of Dermatology, 2016 Oct; 75(4), p. 831-834.
PMID: 27646740
Related Citations

Alcohol Intake is Associated with Increased Risk of Squamous Cell Carcinoma of the Skin: Three US Prospective Cohort Studies.
Authors: Siiskonen S. , Han J. , Li T. , Cho E. , Nijsten T. , Qureshi A. .
Source: Nutrition and cancer, 2016 May-Jun; 68(4), p. 545-553.
EPub date: 2016-05-04.
PMID: 27145335
Related Citations

History of Severe Sunburn and Risk of Skin Cancer Among Women and Men in 2 Prospective Cohort Studies.
Authors: Wu S. , Cho E. , Li W.Q. , Weinstock M.A. , Han J. , Qureshi A.A. .
Source: American journal of epidemiology, 2016-05-01; 183(9), p. 824-33.
EPub date: 2016-04-03.
PMID: 27045074
Related Citations

Reply to S. Lehrer et al and J.C. Dowdy and R.M. Sayre.
Authors: Wu S. , Cho E. , Qureshi A.A. .
Source: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2016-02-20; 34(6), p. 637-8.
EPub date: 2016-01-04.
PMID: 26729435
Related Citations

Vitamin D Intake and Risk of Skin Cancer in US Women and Men.
Authors: Park S.M. , Li T. , Wu S. , Li W.Q. , Qureshi A.A. , Cho E. .
Source: PloS one, 2016; 11(8), p. e0160308.
EPub date: 2016-08-24.
PMID: 27557122
Related Citations

Alcohol consumption and risk of cutaneous basal cell carcinoma in women and men: 3 prospective cohort studies.
Authors: Wu S. , Li W.Q. , Qureshi A.A. , Cho E. .
Source: The American journal of clinical nutrition, 2015 Nov; 102(5), p. 1158-66.
EPub date: 2015-09-30.
PMID: 26423390
Related Citations

Use of permanent hair dyes and risk of vitiligo in women.
Authors: Wu S. , Li W.Q. , Cho E. , Harris J.E. , Speizer F. , Qureshi A.A. .
Source: Pigment cell & melanoma research, 2015 Nov; 28(6), p. 744-6.
EPub date: 2015-08-20.
PMID: 26212072
Related Citations

Caffeine Intake, Coffee Consumption, and Risk of Cutaneous Malignant Melanoma.
Authors: Wu S. , Han J. , Song F. , Cho E. , Gao X. , Hunter D.J. , Qureshi A.A. .
Source: Epidemiology (Cambridge, Mass.), 2015 Nov; 26(6), p. 898-908.
PMID: 26172864
Related Citations

Citrus Consumption and Risk of Cutaneous Malignant Melanoma.
Authors: Wu S. , Han J. , Feskanich D. , Cho E. , Stampfer M.J. , Willett W.C. , Qureshi A.A. .
Source: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2015-08-10; 33(23), p. 2500-8.
EPub date: 2015-06-29.
PMID: 26124488
Related Citations

Alcohol intake and risk of incident psoriatic arthritis in women.
Authors: Wu S. , Cho E. , Li W.Q. , Han J. , Qureshi A.A. .
Source: The Journal of rheumatology, 2015 May; 42(5), p. 835-40.
EPub date: 2015-04-01.
PMID: 25834201
Related Citations

Association between BRAFV600E and NRASQ61R mutations and clinicopathologic characteristics, risk factors and clinical outcome of primary invasive cutaneous melanoma.
Authors: Wu S. , Kuo H. , Li W.Q. , Canales A.L. , Han J. , Qureshi A.A. .
Source: Cancer causes & control : CCC, 2014 Oct; 25(10), p. 1379-86.
EPub date: 2014-07-22.
PMID: 25048604
Related Citations

Long-term ultraviolet flux, other potential risk factors, and skin cancer risk: a cohort study.
Authors: Wu S. , Han J. , Laden F. , Qureshi A.A. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2014 Jun; 23(6), p. 1080-9.
PMID: 24876226
Related Citations

Cumulative ultraviolet radiation flux in adulthood and risk of incident skin cancers in women.
Authors: Wu S. , Han J. , Vleugels R.A. , Puett R. , Laden F. , Hunter D.J. , Qureshi A.A. .
Source: British journal of cancer, 2014-04-02; 110(7), p. 1855-61.
EPub date: 2014-03-04.
PMID: 24595003
Related Citations

CXCR4 pathway associated with family history of melanoma.
Authors: Li W.Q. , Han J. , Widlund H.R. , Correll M. , Wang Y.E. , Quackenbush J. , Mihm M.C. , Canales A.L. , Wu S. , Golub T. , et al. .
Source: Cancer causes & control : CCC, 2014 Jan; 25(1), p. 125-32.
EPub date: 2013-10-25.
PMID: 24158781
Related Citations

Use of tanning beds and incidence of skin cancer.
Authors: Zhang M. , Qureshi A.A. , Geller A.C. , Frazier L. , Hunter D.J. , Han J. .
Source: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2012-05-10; 30(14), p. 1588-93.
EPub date: 2012-02-27.
PMID: 22370316
Related Citations

Obesity and the incidence of skin cancer in US Caucasians.
Authors: Pothiawala S. , Qureshi A.A. , Li Y. , Han J. .
Source: Cancer causes & control : CCC, 2012 May; 23(5), p. 717-26.
EPub date: 2012-03-27.
PMID: 22450736
Related Citations

Integrating pathway analysis and genetics of gene expression for genome-wide association study of basal cell carcinoma.
Authors: Zhang M. , Liang L. , Morar N. , Dixon A.L. , Lathrop G.M. , Ding J. , Moffatt M.F. , Cookson W.O. , Kraft P. , Qureshi A.A. , et al. .
Source: Human genetics, 2012 Apr; 131(4), p. 615-23.
EPub date: 2011-10-18.
PMID: 22006220
Related Citations

Exonuclease 1 (EXO1) gene variation and melanoma risk.
Authors: Song F. , Qureshi A.A. , Zhang J. , Zhan J. , Amos C.I. , Lee J.E. , Wei Q. , Han J. .
Source: DNA repair, 2012-03-01; 11(3), p. 304-9.
EPub date: 2012-01-09.
PMID: 22230721
Related Citations

Genome-wide association study identifies novel loci predisposing to cutaneous melanoma.
Authors: Amos C.I. , Wang L.E. , Lee J.E. , Gershenwald J.E. , Chen W.V. , Fang S. , Kosoy R. , Zhang M. , Qureshi A.A. , Vattathil S. , et al. .
Source: Human molecular genetics, 2011-12-15; 20(24), p. 5012-23.
EPub date: 2011-09-17.
PMID: 21926416
Related Citations

Sunlight exposure, vitamin D, and risk of non-Hodgkin lymphoma in the Nurses' Health Study.
Authors: Bertrand K.A. , Chang E.T. , Abel G.A. , Zhang S.M. , Spiegelman D. , Qureshi A.A. , Laden F. .
Source: Cancer causes & control : CCC, 2011 Dec; 22(12), p. 1731-41.
EPub date: 2011-10-11.
PMID: 21987081
Related Citations

Shorter telomeres associate with a reduced risk of melanoma development.
Authors: Nan H. , Du M. , De Vivo I. , Manson J.E. , Liu S. , McTiernan A. , Curb J.D. , Lessin L.S. , Bonner M.R. , Guo Q. , et al. .
Source: Cancer research, 2011-11-01; 71(21), p. 6758-63.
EPub date: 2011-10-25.
PMID: 22028319
Related Citations

No association between telomere length in peripheral blood leukocytes and the risk of nonmelanoma skin cancer.
Authors: Liang G. , Qureshi A.A. , Guo Q. , De Vivo I. , Han J. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2011 May; 20(5), p. 1043-5.
EPub date: 2011-02-25.
PMID: 21357377
Related Citations

Rotating night shifts and risk of skin cancer in the nurses' health study.
Authors: Schernhammer E.S. , Razavi P. , Li T.Y. , Qureshi A.A. , Han J. .
Source: Journal of the National Cancer Institute, 2011-04-06; 103(7), p. 602-6.
EPub date: 2011-02-18.
PMID: 21335547
Related Citations

A germline variant in the interferon regulatory factor 4 gene as a novel skin cancer risk locus.
Authors: Han J. , Qureshi A.A. , Nan H. , Zhang J. , Song Y. , Guo Q. , Hunter D.J. .
Source: Cancer research, 2011-03-01; 71(5), p. 1533-9.
EPub date: 2011-01-26.
PMID: 21270109
Related Citations

ASIP genetic variants and the number of non-melanoma skin cancers.
Authors: Lin W. , Qureshi A.A. , Kraft P. , Nan H. , Guo Q. , Hu F.B. , Jensen M.K. , Han J. .
Source: Cancer causes & control : CCC, 2011 Mar; 22(3), p. 495-501.
EPub date: 2011-01-09.
PMID: 21221757
Related Citations

Pathway analysis for genome-wide association study of basal cell carcinoma of the skin.
Authors: Zhang M. , Liang L. , Xu M. , Qureshi A.A. , Han J. .
Source: PloS one, 2011; 6(7), p. e22760.
EPub date: 2011-07-28.
PMID: 21829505
Related Citations

Heterogeneity in host risk factors for incident melanoma and non-melanoma skin cancer in a cohort of US women.
Authors: Qureshi A.A. , Zhang M. , Han J. .
Source: Journal of epidemiology, 2011; 21(3), p. 197-203.
EPub date: 2011-04-23.
PMID: 21515942
Related Citations




Back to Top