Publications by authors named "Padma Sheila Rajagopal"

8 Publications

  • Page 1 of 1

Standards for the classification of pathogenicity of somatic variants in cancer (oncogenicity): Joint recommendations of Clinical Genome Resource (ClinGen), Cancer Genomics Consortium (CGC), and Variant Interpretation for Cancer Consortium (VICC).

Genet Med 2022 05 29;24(5):986-998. Epub 2022 Jan 29.

The University of Texas MD Anderson Cancer Center, Houston, TX.

Purpose: Several professional societies have published guidelines for the clinical interpretation of somatic variants, which specifically address diagnostic, prognostic, and therapeutic implications. Although these guidelines for the clinical interpretation of variants include data types that may be used to determine the oncogenicity of a variant (eg, population frequency, functional, and in silico data or somatic frequency), they do not provide a direct, systematic, and comprehensive set of standards and rules to classify the oncogenicity of a somatic variant. This insufficient guidance leads to inconsistent classification of rare somatic variants in cancer, generates variability in their clinical interpretation, and, importantly, affects patient care. Therefore, it is essential to address this unmet need.

Methods: Clinical Genome Resource (ClinGen) Somatic Cancer Clinical Domain Working Group and ClinGen Germline/Somatic Variant Subcommittee, the Cancer Genomics Consortium, and the Variant Interpretation for Cancer Consortium used a consensus approach to develop a standard operating procedure (SOP) for the classification of oncogenicity of somatic variants.

Results: This comprehensive SOP has been developed to improve consistency in somatic variant classification and has been validated on 94 somatic variants in 10 common cancer-related genes.

Conclusion: The comprehensive SOP is now available for classification of oncogenicity of somatic variants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gim.2022.01.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9081216PMC
May 2022

Whole-genome analysis of Nigerian patients with breast cancer reveals ethnic-driven somatic evolution and distinct genomic subtypes.

Nat Commun 2021 11 26;12(1):6946. Epub 2021 Nov 26.

Center for Clinical Cancer Genetics and Global Health, Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA.

Black women across the African diaspora experience more aggressive breast cancer with higher mortality rates than white women of European ancestry. Although inter-ethnic germline variation is known, differential somatic evolution has not been investigated in detail. Analysis of deep whole genomes of 97 breast cancers, with RNA-seq in a subset, from women in Nigeria in comparison with The Cancer Genome Atlas (n = 76) reveal a higher rate of genomic instability and increased intra-tumoral heterogeneity as well as a unique genomic subtype defined by early clonal GATA3 mutations with a 10.5-year younger age at diagnosis. We also find non-coding mutations in bona fide drivers (ZNF217 and SYPL1) and a previously unreported INDEL signature strongly associated with African ancestry proportion, underscoring the need to expand inclusion of diverse populations in biomedical research. Finally, we demonstrate that characterizing tumors for homologous recombination deficiency has significant clinical relevance in stratifying patients for potentially life-saving therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-27079-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626467PMC
November 2021

Telomere biology disorder prevalence and phenotypes in adults with familial hematologic and/or pulmonary presentations.

Blood Adv 2020 10;4(19):4873-4886

Section of Hematology/Oncology and Center for Clinical Cancer Genetics and.

Telomere biology disorders (TBDs) present heterogeneously, ranging from infantile bone marrow failure associated with very short telomeres to adult-onset interstitial lung disease (ILD) with normal telomere length. Yield of genetic testing and phenotypic spectra for TBDs caused by the expanding list of telomere genes in adults remain understudied. Thus, we screened adults aged ≥18 years with a personal and/or family history clustering hematologic disorders and/or ILD enrolled on The University of Chicago Inherited Hematologic Disorders Registry for causative variants in 13 TBD genes. Sixteen (10%) of 153 probands carried causative variants distributed among TERT (n = 6), TERC (n = 4), PARN (n = 5), or RTEL1 (n = 1), of which 19% were copy number variants. The highest yield (9 of 22 [41%]) was in families with mixed hematologic and ILD presentations, suggesting that ILD in hematology populations and hematologic abnormalities in ILD populations warrant TBD genetic testing. Four (3%) of 117 familial hematologic disorder families without ILD carried TBD variants, making TBD second to only DDX41 in frequency for genetic diagnoses in this population. Phenotypes of 17 carriers with heterozygous PARN variants included 4 (24%) with hematologic abnormalities, 67% with lymphocyte telomere lengths measured by flow cytometry and fluorescence in situ hybridization at or above the 10th percentile, and a high penetrance for ILD. Alternative etiologies for cytopenias and/or ILD such as autoimmune features were noted in multiple TBD families, emphasizing the need to maintain clinical suspicion for a TBD despite the presence of alternative explanations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/bloodadvances.2020001721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556157PMC
October 2020

Black Lives Matter Worldwide: Retooling Precision Oncology for True Equity of Cancer Care.

Cell Rep Med 2020 08;1(5):100079

Section of Hematology/Oncology, Department of Medicine, University of Chicago Medical Center, Chicago, IL 60637, USA.

In a recent issue of , Carrot-Zhang et al. identified ancestry-specific molecular variants and expression changes among patients from The Cancer Genome Atlas (TCGA). Their study findings and limitations highlight the critical need to diversify populations represented in cancer genomics research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.xcrm.2020.100079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446667PMC
August 2020

USPSTF Recommendations for BRCA1 and BRCA2 Testing in the Context of a Transformative National Cancer Control Plan.

JAMA Netw Open 2019 08 2;2(8):e1910142. Epub 2019 Aug 2.

Center for Clinical Cancer Genetics, The University of Chicago, Chicago, Illinois.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamanetworkopen.2019.10142DOI Listing
August 2019

The Time for Mainstreaming Germline Testing for Patients With Breast Cancer Is Now.

J Clin Oncol 2019 08 27;37(24):2177-2178. Epub 2019 Jun 27.

Padma Sheila Rajagopal, MD, MPH; Daniel V.T. Catenacci, MD; and Olufunmilayo I. Olopade, MD, University of Chicago Medical Center, Chicago, IL.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.19.00160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6698918PMC
August 2019

Employment trends in young women following a breast cancer diagnosis.

Breast Cancer Res Treat 2019 Aug 30;177(1):207-214. Epub 2019 May 30.

Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02215, USA.

Purpose: Little is known about how a breast cancer diagnosis and treatment affects job-related outcomes in young women with breast cancer, who are an integral part of the workforce. We sought to describe employment trends among young breast cancer survivors.

Methods: 911 women with non-metastatic breast cancer were surveyed about employment-related outcomes 1 year post-diagnosis. Participants were enrolled in the Young Women's Breast Cancer Study an ongoing, multi-center cohort of women diagnosed with breast cancer at age ≤ 40.

Results: Among 911 women, median age at diagnosis was 36 years (range 17-40). Most women (80%, n = 729) were employed 1 year post-diagnosis. Among the 7% (n = 62) employed before diagnosis but who reported unemployment at 1 year, approximately half reported they were unemployed for health reasons. Among employed women, 7% said treatment affected their ability to perform their job. Women with stage-three disease (vs. stage 1 disease, odds ratio (OR): 3.73, 95% CI 1.39-9.97) and those who reported having money to pay bills after cutting back or difficulty paying bills at baseline (vs. having enough money for special things, OR 2.70, 95% CI 1.32-5.52) at baseline were more likely to have transitioned out of the workforce.

Conclusions: Our results suggest an impact of disease burden and socioeconomic status on employment in young breast cancer survivors. There is a need to ensure young survivors who leave the workforce following diagnosis are sufficiently supported given the potential adverse psychosocial and financial impacts of unemployment on survivors, their families, communities, and society.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10549-019-05293-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265819PMC
August 2019

Chemotherapy for advanced cancers.

Ann Palliat Med 2014 Jul;3(3):203-28

Dana-Farber Cancer Institute, Boston, MA, 450 Brookline Ave, Boston, MA 02215, USA.

The decision to treat with chemotherapy in advanced cancers is a complex process that requires oncologists to weigh the indications and benefits. Treatment of patients with advanced cancer is typically multidimensional and should ideally include oncologists in coordination with palliative care specialists. When the intent of chemotherapy for patients with advanced neoplasms is no longer curative, palliative care can and should be delivered simultaneously with antineoplastic agents. Often, chemotherapy for advanced cancers is delivered in an attempt to palliate symptoms, and therefore improve quality of life (QOL). The role of palliative chemotherapy should be continually reevaluated throughout the trajectory of the patient's illness. When chemotherapy is no longer controlling the disease or helping symptoms, the role of chemotherapy should be reconsidered. This review aims to provide a foundation for discussions about treatment of patients with advanced malignancies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3978/j.issn.2224-5820.2014.06.02DOI Listing
July 2014
-->