Publications by authors named "Lisa Zaba"

50 Publications

Dermatologic toxicities of targeted antineoplastic agents and immune checkpoint inhibitor therapy in pediatric patients: A systematic review.

Pediatr Blood Cancer 2021 Sep 26:e29346. Epub 2021 Sep 26.

Department of Dermatology, Stanford University School of Medicine, Stanford, California, USA.

Cutaneous adverse events (cAEs) from targeted antineoplastic agents and immune checkpoint inhibitors are common in children with cancer and may lead to dose reduction or cessation of critical oncologic treatment. Timely diagnosis and proper management of cAEs in pediatric oncology patients is essential to optimize ongoing cancer-directed therapy and improve quality of life. This systematic review of published studies summarizes dermatologic toxicities to targeted anticancer treatments and immune checkpoint inhibitors.
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http://dx.doi.org/10.1002/pbc.29346DOI Listing
September 2021

Clinical features of drug-induced hypersensitivity syndrome to BRAF inhibitors with and without previous immune checkpoint inhibition: a review.

Support Care Cancer 2021 Sep 21. Epub 2021 Sep 21.

Department of Dermatology, Stanford University Medical Center and Cancer Institute, 780 Welch Road, CJ220F, Palo Alto, CA, 94304-5779, USA.

Purpose: Cutaneous reactions to BRAF inhibitors are common, but severe reactions resembling or consistent with drug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) are relatively rare. Several reports suggest that cutaneous reactions including DRESS/DIHS to BRAF inhibitors are more frequent and severe in the setting of previous immune checkpoint inhibition (ICI).

Methods: To characterize existing literature on these reports, we queried the PubMed/MEDLINE database for cases of DIHS/DRESS to BRAF inhibitors.

Results: We identified 23 cases of DIHS to BRAF inhibitors following checkpoint inhibition and 14 cases without prior checkpoint inhibitor therapy. In both cohorts, DIHS occurred relatively early, with median time to onset from drug exposure of 8-10 days. Patients who received prior ICI were less likely to have peripheral eosinophilia (26% vs 71%), atypical lymphocytes (9% vs 50%), renal involvement (61% vs 79%), hepatic involvement (52% vs 86%), and lymphadenopathy (9% vs 43%) compared to patients who did not receive prior ICI. Thrombocytopenia was more common with prior ICI (17% vs 7%). Only patients who received prior ICI experienced hypotension (26%) during the course of their DIHS. All cases of BRAF-induced DIHS generally improved on systemic steroids/supportive care, and no cases of death were identified.

Conclusion: Dermatologists should consider a diagnosis of DIHS following BRAF inhibitor initiation, particularly in the setting of past checkpoint inhibition, with atypical features including relatively rapid onset and steroid responsiveness, lack of peripheral eosinophilia, lymphocytosis, or lymphadenopathy, and increased risk of thrombocytopenia and hypotension.
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http://dx.doi.org/10.1007/s00520-021-06543-9DOI Listing
September 2021

Risk factors for and prognostic impact of positive surgical margins after excision of Merkel cell carcinoma.

J Am Acad Dermatol 2021 Sep 16. Epub 2021 Sep 16.

Veterans Affairs Palo Alto Healthcare System, Palo Alto, California; Department of Dermatology, Stanford University School of Medicine, Palo Alto, California. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2021.09.014DOI Listing
September 2021

Synergistic effect of lymphovascular invasion and nodal involvement on prognosis in Merkel cell carcinoma: A retrospective analysis in the National Cancer Database.

J Am Acad Dermatol 2021 Sep 7. Epub 2021 Sep 7.

Veterans Affairs Palo Alto Healthcare System, Palo Alto, California; Department of Dermatology, Stanford University School of Medicine, Palo Alto, California. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2021.08.055DOI Listing
September 2021

Prognostic value of lymphovascular invasion in early-stage Merkel cell carcinoma: A retrospective analysis in the National Cancer Database.

J Am Acad Dermatol 2021 Jul 20. Epub 2021 Jul 20.

Veterans Affairs Palo Alto Healthcare System, Palo Alto, California; Department of Dermatology, Stanford University School of Medicine, Palo Alto, California. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2021.07.018DOI Listing
July 2021

Merkel cell carcinoma patients with solid organ transplant or hematologic malignancy: Demographics, survival, and prognosticators.

J Am Acad Dermatol 2021 May 31. Epub 2021 May 31.

Veterans Affairs Palo Alto Healthcare System, Palo Alto, California; Department of Dermatology, Stanford University School of Medicine, Palo Alto, California. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2021.05.042DOI Listing
May 2021

Rare and fatal complication of immune checkpoint inhibition: a case report of haemophagocytic lymphohistiocytosis with severe lichenoid dermatitis.

Br J Haematol 2021 06 5;193(6):e44-e47. Epub 2021 May 5.

Department of Dermatology, Stanford Hospitals and Clinics, Stanford, CA, USA.

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http://dx.doi.org/10.1111/bjh.17442DOI Listing
June 2021

Prognostic Value of Bone Marrow Metabolism on Pretreatment F-FDG PET/CT in Patients with Metastatic Melanoma Treated with Anti-PD-1 Therapy.

J Nucl Med 2021 Oct 5;62(10):1380-1383. Epub 2021 Feb 5.

Department of Radiology, Stanford University, Stanford, California.

Our purpose was to investigate the prognostic value of F-FDG PET/CT parameters in melanoma patients before beginning therapy with antibodies to the programmed cell death 1 receptor (anti-PD-1). Imaging parameters including SUV, metabolic tumor volume, and the ratio of bone marrow to liver SUV (BLR) were measured from baseline PET/CT in 92 patients before the start of anti-PD-1 therapy. The association with survival and imaging parameters combined with clinical factors was evaluated. Clinical and laboratory data were compared between the high-BLR group (>median) and the low-BLR group (≤median). Multivariate analyses demonstrated that BLR was an independent prognostic factor for progression-free and overall survival ( = 0.017 and = 0.011, respectively). The high-BLR group had higher white blood cell counts and neutrophil counts and a higher level of C-reactive protein than the low-BLR group ( < 0.05). Patients with a high BLR were associated with poor progression-free and overall survival, potentially explained by evidence of systemic inflammation known to be associated with immunosuppression.
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http://dx.doi.org/10.2967/jnumed.120.254482DOI Listing
October 2021

Cutaneous cytomegalovirus - A case of disseminated cytomegalovirus presenting with extensive ulcerative skin lesions in a renal transplant recipient.

Transpl Infect Dis 2021 Aug 16;23(4):e13582. Epub 2021 Feb 16.

Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.

Cytomegalovirus (CMV) reactivation is common in organ transplant recipients and can lead to significant morbidity and mortality. Cutaneous CMV findings are rarely reported in the literature and diagnosis can be delayed if not clinically recognized. We describe a case of a female patient 20 years post renal transplant who presented with extensive ulcerative skin lesions and diarrhea. She rapidly deteriorated and died on day 5 of hospitalization. Autopsy noted extensive CMV involvement of skin and gastrointestinal (GI) tract by CMV-specific immunohistochemistry. These findings, along with high-grade CMV viremia, led to the final postmortem diagnosis of disseminated CMV infection. This case focuses on the cutaneous findings of disseminated CMV as recognition of CMV skin lesions can lead to earlier initiation of appropriate therapy in transplant recipients.
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http://dx.doi.org/10.1111/tid.13582DOI Listing
August 2021

How we treat Merkel cell carcinoma: within and beyond current guidelines.

Future Oncol 2021 Apr 29;17(11):1363-1377. Epub 2021 Jan 29.

Division of Dermatology, University of Washington at South Lake Union, Seattle, WA 98109, USA.

Merkel cell carcinoma (MCC) is an aggressive skin cancer associated with a high risk of local recurrence and distant metastasis. Optimal care of this potentially life-threatening cancer is critical but challenging because: physicians are often unfamiliar with its management due to rarity, and MCC management remains controversial, in part because it is rapidly evolving across multiple specialties. While guidelines offer a broad overview of management, they are often not sufficient when making decisions for individual patients. Herein, we present a literature review as well as practical approaches adopted at our institutions for staging, surveillance and therapy of MCC. Each of these areas are discussed in light of how they can be appropriately customized for prevalent but challenging situations. We also provide representative examples of MCC patient scenarios and how they were managed by a multidisciplinary team to identify suitable evidence-based, individualized treatment plans.
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http://dx.doi.org/10.2217/fon-2020-1036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983043PMC
April 2021

Chromatin accessibility landscapes of skin cells in systemic sclerosis nominate dendritic cells in disease pathogenesis.

Nat Commun 2020 11 17;11(1):5843. Epub 2020 Nov 17.

Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA, USA.

Systemic sclerosis (SSc) is a disease at the intersection of autoimmunity and fibrosis. However, the epigenetic regulation and the contributions of diverse cell types to SSc remain unclear. Here we survey, using ATAC-seq, the active DNA regulatory elements of eight types of primary cells in normal skin from healthy controls, as well as clinically affected and unaffected skin from SSc patients. We find that accessible DNA elements in skin-resident dendritic cells (DCs) exhibit the highest enrichment of SSc-associated single-nucleotide polymorphisms (SNPs) and predict the degrees of skin fibrosis in patients. DCs also have the greatest disease-associated changes in chromatin accessibility and the strongest alteration of cell-cell interactions in SSc lesions. Lastly, data from an independent cohort of patients with SSc confirm a significant increase of DCs in lesioned skin. Thus, the DCs epigenome links inherited susceptibility and clinically apparent fibrosis in SSc skin, and can be an important driver of SSc pathogenesis.
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http://dx.doi.org/10.1038/s41467-020-19702-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672105PMC
November 2020

Prognostic value of volumetric PET parameters at early response evaluation in melanoma patients treated with immunotherapy.

Eur J Nucl Med Mol Imaging 2020 11 15;47(12):2787-2795. Epub 2020 Apr 15.

Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Stanford University, 300 Pasteur Drive, Stanford, CA, 94305-5281, USA.

Purpose: The purpose of this study was to investigate the prognostic value of whole-body metabolic tumor volume (MTV) and other metabolic tumor parameters, obtained from baseline and first restaging F-FDG PET/CT scans in melanoma patients treated with immune checkpoint inhibitors (ICIs).

Methods: Eighty-five consecutive melanoma patients (M, 57; F, 28) treated with ICIs who underwent PET/CT scans before and approximately 3 months after the start of immunotherapy were retrospectively enrolled. Metabolic tumor parameters including MTV for all melanoma lesions were measured on each scan. A Cox proportional hazards model was used for univariate and multivariate analyses of metabolic parameters combined with known clinical prognostic factors associated with overall survival (OS). Kaplan-Meier curves for patients dichotomized based on median values of imaging parameters were generated.

Results: The median OS time in all patients was 45 months (95% CI 24-45 months). Univariate analysis demonstrated that MTV obtained from first restaging PET/CT scans (MTVpost) was the strongest prognostic factor for OS among PET/CT parameters (P < 0.0001). The median OS in patients with high MTVpost (≥ 23.44) was 16 months (95% CI 12-32 months) as compared with more than 60 months in patients with low MTVpost (< 23.44) (P = 0.0003). A multivariate model including PET/CT parameters and known clinical prognostic factors revealed that MTVpost and the presence of central nervous system lesions were independent prognostic factors for OS (P = 0.0004, 0.0167, respectively). One pseudoprogression case (1.2%) was seen in this population and classified into the high MTVpost group.

Conclusion: Whole-body metabolic tumor volume from PET scan acquired approximately 3 months following initiation of immunotherapy (MTVpost) is a strong prognostic indicator of OS in melanoma patients. Although the possibility of pseudoprogression must be considered whenever evaluating first restaging PET imaging, it only occurred in 1 patient in our cohort.
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http://dx.doi.org/10.1007/s00259-020-04792-0DOI Listing
November 2020

Increased Mortality in Asians With Systemic Sclerosis in Northern California.

ACR Open Rheumatol 2020 Apr 21;2(4):197-206. Epub 2020 Mar 21.

Stanford University School of Medicine and Department of Veterans Affairs Palo Alto Health Care System, Palo Alto, California.

Objective: The objective of this study is to evaluate racial/ethnic differences in disease manifestations and survival in a US cohort of patients with systemic sclerosis (SSc), with a focus on Asian patients.

Methods: A retrospective cohort study was conducted among Kaiser Permanente Northern California adults with an incident SSc diagnosis by a rheumatologist from 2007 to 2016, confirmed by a chart review to fulfill 2013 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria. Self-reported race/ethnicity was categorized as non-Hispanic white, Asian, Hispanic, and black. Disease manifestations and survival were compared, using white patients as the reference.

Results: A total of 609 patients with incident SSc were identified: 89% were women, and 81% had limited cutaneous SSc, with a mean age at diagnosis of 55.4 ± 14.8 years. The racial/ethnic distribution was 51% non-Hispanic white (n = 310), 25% Hispanic (n = 154), 16% Asian (n = 96), and 8% black (n = 49). Compared with white patients, black patients had a greater prevalence of diffuse disease (14.5% vs. 44.9%; P < 0.001), and Asians had higher rates of anti-U1-RNP antibodies (32.1% vs. 11.9%; P = 0.005). Nine-year overall survival rates following SSc diagnosis were lower in Asian (52.3%), black (52.2%), and Hispanic patients (68.2%) compared with white patients (75.8%). Pulmonary hypertension and infections were the leading causes of death in Asian patients. Asian race was associated with higher mortality on univariable (hazard ratio [HR] 1.83 [95% confidence interval (CI) 1.08-2.99]; P = 0.020) and multivariable analyses (HR 1.80 [95% CI 0.99-3.16]; P = 0.047) when adjusting for age, sex, body mass index, cutaneous subtype, smoking status, interstitial lung disease, pulmonary hypertension, renal crisis, and malabsorption syndrome.

Conclusion: Asian patients with SSc in this US cohort had increased mortality compared with white patients. These patients warrant close monitoring for disease progression.
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http://dx.doi.org/10.1002/acr2.11126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164633PMC
April 2020

Cutaneous pleomorphic fibromas arising in patients with germline TP53 mutations.

J Cutan Pathol 2020 Aug 6;47(8):734-741. Epub 2020 Apr 6.

Department of Pathology, Stanford University School of Medicine, Stanford, California.

Pleomorphic fibromas are rare benign cutaneous neoplasms associated with deletion/loss of chromosomes 13q and 17p, where RB1 and TP53 are located, respectively. Herein, we report five cases of pleomorphic fibroma arising in patients with germline TP53 mutations, suggesting a potential link with Li-Fraumeni syndrome. All three patients were female and young (mean age 27) with a strong personal and/or family oncologic history and confirmed pathogenic germline TP53 mutations. In two patients, multiple pleomorphic fibromas were diagnosed. Clinically, the lesions arose at various cutaneous sites and were small (≤2 cm) and raised (4/5). Histopathologically, the tumors were paucicellular, composed of atypical spindled to stellate cells with hyperchromatic and variably pleomorphic nuclei. Mitotic activity was exceedingly low, although rare atypical mitotic figures were seen in one case. Immunohistochemically, the tumor cells were diffusely positive for p16 (3/3) and showed loss of Rb expression (5/5). All cases showed aberrant p53 expression (overexpression in 4, complete loss in 1). The tumors have followed a benign clinical course with no evidence of progression or recurrence. In conclusion, the development of multiple pleomorphic fibromas in a young patient may be a clue to an underlying genetic cancer syndrome involving TP53.
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http://dx.doi.org/10.1111/cup.13686DOI Listing
August 2020

A persistent dermal hypersensitivity reaction associated with infection.

JAAD Case Rep 2020 Feb 30;6(2):156-158. Epub 2020 Jan 30.

Department of Dermatology, State University of New York Downstate Medical Center, Brooklyn, New York.

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http://dx.doi.org/10.1016/j.jdcr.2019.11.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6997649PMC
February 2020

Chromatin Accessibility Landscape of Cutaneous T Cell Lymphoma and Dynamic Response to HDAC Inhibitors.

Cancer Cell 2017 07 15;32(1):27-41.e4. Epub 2017 Jun 15.

Center for Personal Dynamic Regulomes and Program in Epithelial Biology, Stanford University School of Medicine, CCSR 2155c, 269 Campus Drive, Stanford, CA 94305-5168, USA; Department of Dermatology, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address:

Here, we define the landscape and dynamics of active regulatory DNA in cutaneous T cell lymphoma (CTCL) by ATAC-seq. Analysis of 111 human CTCL and control samples revealed extensive chromatin signatures that distinguished leukemic, host, and normal CD4 T cells. We identify three dominant patterns of transcription factor (TF) activation that drive leukemia regulomes, as well as TF deactivations that alter host T cells in CTCL patients. Clinical response to histone deacetylase inhibitors (HDACi) is strongly associated with a concurrent gain in chromatin accessibility. HDACi causes distinct chromatin responses in leukemic and host CD4 T cells, reprogramming host T cells toward normalcy. These results provide a foundational framework to study personal regulomes in human cancer and epigenetic therapy.
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http://dx.doi.org/10.1016/j.ccell.2017.05.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5559384PMC
July 2017

Individuality and variation of personal regulomes in primary human T cells.

Cell Syst 2015 Jul;1(1):51-61

Howard Hughes Medical Institute and Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305.

Here we survey variation and dynamics of active regulatory elements genome-wide using longitudinal samples from human individuals. We applied Assay of Transposase Accessible Chromatin with sequencing (ATAC-seq) to map chromatin accessibility in primary CD4+ T cells isolated from standard blood draws of 12 healthy volunteers over time, from cancer patients, and during T cell activation. Over 4,000 predicted regulatory elements (7.2%) showed reproducible variation in accessibility between individuals. Gender was the most significant attributable source of variation. ATAC-seq revealed previously undescribed elements that escape X chromosome inactivation and predicted gender-specific gene regulatory networks across autosomes, which coordinately affect genes with immune function. Noisy regulatory elements with personal variation in accessibility are significantly enriched for autoimmune disease loci. Over one third of regulome variation lacked genetic variation in cis, suggesting contributions from environmental or epigenetic factors. These results refine concepts of human individuality and provide a foundational reference for comparing disease-associated regulomes.
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http://dx.doi.org/10.1016/j.cels.2015.06.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4522940PMC
July 2015

Distinctive cutaneous and systemic features associated with antitranscriptional intermediary factor-1γ antibodies in adults with dermatomyositis.

J Am Acad Dermatol 2015 Mar 14;72(3):449-55. Epub 2015 Jan 14.

Johns Hopkins University School of Medicine, Division of Rheumatology, Baltimore, Maryland.

Background: Antibodies against transcriptional intermediary factor (TIF)-1γ are associated with malignancy in dermatomyositis (DM). Identification of clinical findings associated with anti-TIF-1γ antibodies in DM is a high priority for both patient diagnosis and risk assessment.

Objective: We sought to define the clinical phenotype of patients with anti-TIF-1γ DM.

Methods: Using a novel, sensitive, and specific assay for anti-TIF-1γ antibodies, we retrospectively tested plasma from 134 adult patients with DM and examined associations between anti-TIF-1γ antibodies and particular clinical and laboratory features.

Results: In all, 55 (41%) patients had autoantibodies to TIF-1γ. Anti-TIF-1γ positive patients were less likely to have systemic features including interstitial lung disease, Raynaud phenomenon, and arthritis/arthralgia. Patients with TIF-1γ autoantibodies had more extensive skin involvement, and some patients manifested characteristic findings including palmar hyperkeratotic papules, psoriasis-like lesions and a novel finding of hypopigmented and telangiectatic ("red on white") patches.

Limitations: This was a retrospective study from a single tertiary referral center.

Conclusion: TIF-1γ is the most commonly targeted DM-specific autoantigen in adults in a large US cohort. Although these patients tend to have less systemic involvement, their skin disease is often extensive and characteristic. Recognition of cutaneous findings in anti-TIF-1γ positive patients may allow more accurate and timely diagnosis and effective treatment of patients with DM.
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http://dx.doi.org/10.1016/j.jaad.2014.12.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4351728PMC
March 2015

CARD14 expression in dermal endothelial cells in psoriasis.

PLoS One 2014 4;9(11):e111255. Epub 2014 Nov 4.

Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, United States of America.

Mutations in the caspase recruitment domain, family member 14 (CARD14) gene have recently been described in psoriasis patients, and explain the psoriasis susceptibility locus 2 (PSORS2). CARD14 is a scaffolding protein that regulates NF-κB activation, and psoriasis-associated CARD14 mutations lead to enhanced NF-κB signaling. CARD14 is expressed mainly in epidermal keratinocytes, but also in unidentified dermal cells. In this manuscript, the identity of the dermal cell types expressing CARD14, as well the potential functional consequence of overactive CARD14 in these dermal cell types, was determined. Using two-color immunofluorescence, dermal CARD14 did not co-localize with T-cells, dendritic cells, or macrophages. However, dermal CARD14 did highly co-localize with CD31(+) endothelial cells (ECs). CARD14 was also expressed non-dermal endothelial cells, such as aortic endothelial cells, which may indicate a role of CARD14(+)ECs in the systemic inflammation and cardiovascular comorbidities associated with psoriasis. Additionally, phosphorylated NF-κB was found in psoriatic CARD14(+) CD31(+) ECs, demonstrating this pathway is active in dermal ECs in psoriasis. Transfection of dermal ECs with psoriasis-associated CARD14 mutations resulted in increased expression of several chemokines, including CXCL10, IL-8, and CCL2. These results provide preliminary evidence that CARD14 expression in ECs may contribute to psoriasis through increased expression of chemokines and facilitating recruitment of immune cells into skin.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0111255PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4219711PMC
July 2015

Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position.

Nat Methods 2013 Dec 6;10(12):1213-8. Epub 2013 Oct 6.

1] Department of Genetics, Stanford University School of Medicine, Stanford, California, USA. [2] Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California, USA. [3] Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California, USA.

We describe an assay for transposase-accessible chromatin using sequencing (ATAC-seq), based on direct in vitro transposition of sequencing adaptors into native chromatin, as a rapid and sensitive method for integrative epigenomic analysis. ATAC-seq captures open chromatin sites using a simple two-step protocol with 500-50,000 cells and reveals the interplay between genomic locations of open chromatin, DNA-binding proteins, individual nucleosomes and chromatin compaction at nucleotide resolution. We discovered classes of DNA-binding factors that strictly avoided, could tolerate or tended to overlap with nucleosomes. Using ATAC-seq maps of human CD4(+) T cells from a proband obtained on consecutive days, we demonstrated the feasibility of analyzing an individual's epigenome on a timescale compatible with clinical decision-making.
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http://dx.doi.org/10.1038/nmeth.2688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3959825PMC
December 2013

Most patients with cancer-associated dermatomyositis have antibodies to nuclear matrix protein NXP-2 or transcription intermediary factor 1γ.

Arthritis Rheum 2013 Nov;65(11):2954-62

Stanford University School of Medicine, Stanford, California.

Objective: Since dermatomyositis (DM) is associated with an increased risk of malignancy, accurate identification of patients likely to harbor cancers is important. Using immunoprecipitations from radiolabeled cell lysates, several groups recently showed that anti-transcription intermediary factor 1γ (anti-TIF-1γ) antibodies are associated with malignancy in DM. We undertook this study to develop sensitive, specific assays to detect antibodies against TIF-1γ and nuclear matrix protein NXP-2 and to evaluate their association with malignancy in DM.

Methods: To detect anti-TIF-1γ antibodies, immunoprecipitations were performed using lysates made from HeLa cells overexpressing TIF-1γ, with detection by immunoblotting. Anti-NXP-2 antibodies were assayed by immunoprecipitation using (35) S-methionine-labeled NXP-2 generated by in vitro transcription/translation. We analyzed patient sera from DM cohorts seen at the Stanford University Dermatology Clinic (n = 111) and the Johns Hopkins Myositis Center (n = 102).

Results: A total of 17% and 38% of patients had antibodies against NXP-2 and TIF-1γ, respectively. Reactivity against either NXP-2 or TIF-1γ identified 83% of patients with cancer-associated DM. In addition to older age and male sex, cancer was associated with antibodies to NXP-2 or TIF-1γ on multivariate analysis (odds ratio 3.78 [95% confidence interval 1.33-10.8]). Stratification by sex revealed that anti-NXP-2 was specifically associated with cancer in males (odds ratio 5.78 [95% confidence interval 1.35-24.7]).

Conclusion: These studies demonstrate that anti-NXP-2 and anti-TIF-1γ antibodies are frequent DM specificities (found in 55% of patients) and are present in most patients with cancer-associated DM.
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http://dx.doi.org/10.1002/art.38093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4073292PMC
November 2013
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