Kerri E. Rieger, MD PhD

All Publications

• Biomarker discovery analysis: Alterations in p14, p16, p53, and BAP1 expression in nevi, cutaneous melanoma, and metastatic melanoma. Pigment cell & melanoma research Sargen, M. R., Cloutier, J. M., Sarin, K. Y., Rieger, K. E., Chu, P., Swetter, S. M., Novoa, R. A. 2019

  Abstract

  Protein biomarkers for diagnosis and prognosis are currently lacking for melanoma, which predominantly relies on histologic features for diagnosis (cytologic and nuclear pleomorphism, growth pattern) and staging (Breslow depth, ulceration). In many cases, the histology of the primary tumor is an unreliable predictor of tumor behavior, and consequently sentinel lymph node biopsy along with imaging studies are often necessary to predict likelihood of mortality from disease. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/pcmr.12768

  View details for PubMedID 30672662

• Cross-contamination of Pathology Specimens: A Cautionary Tale CUTIS Lewellis, S. W., Roy, K., Gojenola, L., Swetter, S. M., Rieger, K. E. 2018; 102 (4): E12–E14

  View details for Web of Science ID 000447978900005

• Well-Appearing Newborn With a Vesiculobullous Rash at Birth. Pediatrics Stewart, S. E., Lin, J. L., Everhart, J. L., Pham, T. H., Marqueling, A. L., Rieger, K. E., Hilgenberg, S. L. 2018

  Abstract

  A term, appropriate-for-gestational-age, male infant born via normal spontaneous vaginal delivery presented at birth with a full-body erythematous, vesiculobullous rash. He was well-appearing with normal vital signs and hypoglycemia that quickly resolved. His father had a history of herpes labialis. His mother had an episode of herpes zoster during pregnancy and a prolonged rupture of membranes that was adequately treated. The patient underwent a sepsis workup, including 2 attempted but unsuccessful lumbar punctures, and was started on broad-spectrum antibiotics and acyclovir, given concerns about bacterial or viral infection. The rash evolved over the course of several days. Subsequent workup, with particular attention to his history and presentation, led to his diagnosis.

  View details for DOI 10.1542/peds.2017-0236

  View details for PubMedID 29437933

• Pembrolizumab for advanced basal cell carcinoma: an investigator-initiated, proof-of-concept study. Journal of the American Academy of Dermatology Chang, A. L., Tran, D. C., Cannon, J. G., Li, S., Jeng, M., Patel, R., Van der Bokke, L., Pague, A., Brotherton, R., Rieger, K. E., Satpathy, A. T., Yost, K. E., Reddy, S., Sarin, K., Colevas, A. D. 2018

  View details for DOI 10.1016/j.jaad.2018.08.017

  View details for PubMedID 30145186

• Eruptive Keratoacanthomas Associated With Pembrolizumab Therapy. JAMA dermatology Freites-Martinez, A., Kwong, B. Y., Rieger, K. E., Coit, D. G., Colevas, A. D., Lacouture, M. E. 2017

  Abstract

  To our knowledge, there have been no previous reports of eruptive keratoacanthomas (KAs) in patients receiving pembrolizumab.To report the cases of 3 consecutive patients with pembrolizumab-induced eruptive KAs and their management.Case report study of 3 patients from 2 centers with pembrolizumab-treated cancer who all developed eruptive KAs.All 3 patients had AK treatment with clobetasol ointment and intralesional triamcinolone; 2 patients also underwent open superficial cryosurgery.Three consecutive patients with cancer, 2 men and 1 woman (median age, 83 years; range 77-91 years), experienced pembrolizumab-associated eruptive KAs. All patients presented with a sudden onset of multiple lesions on sun-exposed areas of their extremities after a median of 13 months (range, 4-18 months) of pembrolizumab therapy. On lesional biopsy, a lichenoid infiltrate was observed in the underlying dermis, predominantly composed of CD3+ T cells, scattered CD20+ B cells, and relatively few PD-1+ (programmed cell death 1-positive) T cells, an immunophenotypic pattern also observed in other cases of anti-PD-1-induced lichenoid dermatitis. Patients were treated with clobetasol ointment and intralesional triamcinolone, alone or in combination with open superficial cryosurgery. All KAs resolved in all patients, and no new lesions occurred during close follow-up. Pembrolizumab treatment was continued without disruption in all 3 cases, and all patients had complete responses of their primary cancers.Pembrolizumab is used in advanced melanoma, advanced non-small-cell lung cancer, and in head and neck cancer. A variety of dermatologic immune-related adverse events including maculopapular eruption, lichenoid reactions, pruritus, and vitiligo have been described. This case series demonstrates that pembrolizumab therapy may also be associated with eruptive KAs with characteristic dermal inflammation, which improved with corticosteroid treatment (topical and intralesional) alone or in combination with cryosurgery, allowing patients to continue therapy with pembrolizumab.

  View details for DOI 10.1001/jamadermatol.2017.0989

  View details for PubMedID 28467522

• Intraepidermal Type VII Collagen by Immunofluorescence Mapping: A Specific Finding for Bullous Dermolysis of the Newborn. Pediatric dermatology Heinecke, G., Marinkovich, M. P., Rieger, K. E. 2017; 34 (3): 308-314

  Abstract

  Bullous dermolysis of the newborn (BDN) is a subtype of dystrophic epidermolysis bullosa (DEB) characterized by skin fragility and blister formation at birth that typically resolves within the first year of life. Abnormal intraepidermal retention of type VII collagen (C7) has been reported as a characteristic feature of BDN, but few studies have investigated the specificity of this finding.We retrospectively reviewed pathology reports of patients diagnosed with DEB using immunofluorescence mapping from January 2001 to January 2015. For cases describing intraepidermal accumulation of C7, we collected information on patient characteristics, including genetic testing results, clinical outcome, and concurrent electron microscopy findings, where available.Of the 143 cases of DEB with immunofluorescence mapping, eight patients had intracytoplasmic epidermal retention of C7. Of these eight patients, two were lost to follow-up, four had complete resolution of bullae, and two had marked improvement with rare residual bullae. Concurrent electron microscopic findings available for three patients were consistent with BDN.Our review of immunofluorescence mapping findings in patients with DEB found that 5.6% had abnormal intracytoplasmic epidermal retention of C7, a finding previously reported in BDN. All such patients with clinical outcomes available had resolution or marked improvement of bullae, consistent with clinical outcomes expected in BDN.

  View details for DOI 10.1111/pde.13132

  View details for PubMedID 28523885

• Correlates of multiple basal cell carcinoma in a retrospective cohort study: Sex, histologic subtypes, and anatomic distribution. Journal of the American Academy of Dermatology Kuo, K. Y., Batra, P., Cho, H. G., Li, S., Chahal, H. S., Rieger, K. E., Tang, J. Y., Sarin, K. Y. 2017

  View details for DOI 10.1016/j.jaad.2017.02.047

  View details for PubMedID 28392289

• Postzygotic Mutations in Beta-Actin are Associated with Becker's Nevus and Becker's Nevus Syndrome. journal of investigative dermatology Cai, E. D., Sun, B. K., Chiang, A., Rogers, A., Bernet, L., Cheng, B., Teng, J., Rieger, K. E., Sarin, K. Y. 2017

  View details for DOI 10.1016/j.jid.2017.03.017

  View details for PubMedID 28347698

• Incidence ratio of basal cell carcinoma to squamous cell carcinoma equalizes with age. Journal of the American Academy of Dermatology Chahal, H. S., Rieger, K. E., Sarin, K. Y. 2017; 76 (2): 353-354

  View details for DOI 10.1016/j.jaad.2016.08.019

  View details for PubMedID 28089000

• Zosteriform Mycosis Fungoides: A New Clinical Presentation With a Dermatomal Distribution. The American Journal of dermatopathology Rieger, K. E., Kim, J., Kim, Y. H. 2017; 39 (2): e17-e18

  Abstract

  Classic mycosis fungoides (MF) presents with patches and plaques on the trunk and proximal extremities. However, numerous clinicopathologic variants have been described, making diagnosis challenging. Here, the authors report a 21-year-old woman with immunophenotypically and molecularly confirmed MF occurring in a dermatomal distribution. Awareness of this and other rare variants of MF is critical to avoid misdiagnosis.

  View details for DOI 10.1097/DAD.0000000000000652

  View details for PubMedID 28134736

• Basosquamous Carcinoma: Controversy, Advances, and Future Directions. Dermatologic surgery Tan, C. Z., Rieger, K. E., Sarin, K. Y. 2017; 43 (1): 23-31

  Abstract

  Basosquamous carcinoma is a rare cutaneous neoplasm that has caused considerable controversy as to its classification, pathogenesis, and management.To review and summarize current literature on the definition, pathogenesis, incidence, and management of basosquamous carcinoma.Through December 2015, an electronic search of the Pubmed database was performed using combinations of basosquamous carcinoma and metatypical basal cell carcinoma as search terms.A selection of 39 publications including case reports and series, retrospective studies, and systematic reviews of the literature were included. Descriptions of the definition of basosquamous carcinoma, clinical behavior, histopathological characteristics, current treatment therapies, and future advances are summarized.This systematic review provides a comprehensive overview of the current understanding of basosquamous carcinoma. Further study is required to elucidate the mechanisms driving the formation of this aggressive tumor.

  View details for DOI 10.1097/DSS.0000000000000815

  View details for PubMedID 27340741

• Zosteriform Mycosis Fungoides: A New Clinical Presentation With a Dermatomal Distribution. The American Journal of dermatopathology Rieger, K. E., Kim, J., Kim, Y. H. 2016

  Abstract

  Classic mycosis fungoides (MF) presents with patches and plaques on the trunk and proximal extremities. However, numerous clinicopathologic variants have been described, making diagnosis challenging. Here, the authors report a 21-year-old woman with immunophenotypically and molecularly confirmed MF occurring in a dermatomal distribution. Awareness of this and other rare variants of MF is critical to avoid misdiagnosis.

  View details for DOI 10.1097/DAD.0000000000000652

  View details for PubMedID 28157131

• Safety and Wound Outcomes Following Genetically Corrected Autologous Epidermal Grafts in Patients With Recessive Dystrophic Epidermolysis Bullosa. JAMA Siprashvili, Z., Nguyen, N. T., Gorell, E. S., Loutit, K., Khuu, P., Furukawa, L. K., Lorenz, H. P., Leung, T. H., Keene, D. R., Rieger, K. E., Khavari, P., Lane, A. T., Tang, J. Y., Marinkovich, M. P. 2016; 316 (17): 1808-1817

  Abstract

  Recessive dystrophic epidermolysis bullosa (RDEB) is a devastating, often fatal, inherited blistering disorder caused by mutations in the COL7A1 gene encoding type VII collagen. Support and palliation are the only current therapies.To evaluate the safety and wound outcomes following genetically corrected autologous epidermal grafts in patients with RDEB.Single-center phase 1 clinical trial conducted in the United States of 4 patients with severe RDEB with a measured area of wounds suitable for grafting of at least 100 cm2. Patients with undetectable type VII collagen keratinocyte expression were excluded.Autologous keratinocytes isolated from biopsy samples collected from 4 patients with RDEB were transduced with good manufacturing practice-grade retrovirus carrying full-length human COL7A1 and assembled into epidermal sheet grafts. Type VII collagen gene-corrected grafts (approximately 35 cm2) were transplanted onto 6 wounds in each of the patients (n = 24 grafts).The primary safety outcomes were recombination competent retrovirus, cancer, and autoimmune reaction. Molecular correction was assessed as type VII collagen expression measured by immunofluorescence and immunoelectron microscopy. Wound healing was assessed using serial photographs taken at 3, 6, and 12 months after grafting.The 4 patients (mean age, 23 years [range, 18-32 years]) were all male with an estimated body surface area affected with RDEB of 4% to 30%. All 24 grafts were well tolerated without serious adverse events. Type VII collagen expression at the dermal-epidermal junction was demonstrated on the graft sites by immunofluorescence microscopy in 9 of 10 biopsy samples (90%) at 3 months, in 8 of 12 samples (66%) at 6 months, and in 5 of 12 samples (42%) at 12 months, including correct type VII collagen localization to anchoring fibrils. Wounds with recombinant type VII collagen graft sites displayed 75% or greater healing at 3 months (21 intact graft sites of 24 wound sites; 87%), 6 months (16/24; 67%), and 12 months (12/24; 50%) compared with baseline wound sites.In this preliminary study of 4 patients with RDEB, there was wound healing in some type VII collagen gene-corrected grafts, but the response was variable among patients and among grafted sites and generally declined over 1 year. Long-term follow-up is necessary for these patients, and controlled trials are needed with a broader range of patients to better understand the potential long-term efficacy of genetically corrected autologous epidermal grafts.clinicaltrials.gov Identifier: NCT01263379.

  View details for DOI 10.1001/jama.2016.15588

  View details for PubMedID 27802546

• Ovoid Palatal Patch in Dermatomyositis: A Novel Finding Associated With Anti-TIF1? (p155) Antibodies. JAMA dermatology Bernet, L. L., Lewis, M. A., Rieger, K. E., Casciola-Rosen, L., Fiorentino, D. F. 2016; 152 (9): 1049-1051

  View details for DOI 10.1001/jamadermatol.2016.1429

  View details for PubMedID 27224238

• PUF60: a prominent new target of the autoimmune response in dermatomyositis and Sjogren's syndrome ANNALS OF THE RHEUMATIC DISEASES Fiorentino, D. F., Presby, M., Baer, A. N., Petri, M., Rieger, K. E., Soloski, M., Rosen, A., Mammen, A. L., Christopher-Stine, L., Casciola-Rosen, L. 2016; 75 (6): 1145-1151

  Abstract

  Autoantibodies are used clinically to phenotype and subset patients with autoimmune rheumatic diseases. We detected a novel 60 kDa autoantibody specificity by immunoblotting using a dermatomyositis (DM) patient's serum. Our objective was to identify the targeted autoantigen and to evaluate disease specificity and clinical significance of this new autoantibody.A new 60 kDa specificity was detected by immunoblotting HeLa cell lysates. The targeted autoantigen was identified as poly(U)-binding-splicing factor 60 kDa (PUF60) using (i) a human protein array and (ii) two-dimensional gel electrophoresis and liquid chromatography tandem mass spectrometry peptide sequencing. Anti-PUF60 antibodies were assayed by ELISA using sera from patients with primary Sjögren's syndrome (SS; n=84), systemic lupus erythematosus (SLE; n=71), DM (n=267), polymyositis (n=45), inclusion body myositis (n=45) and healthy controls (n=38).PUF60 was identified as a new autoantigen. Anti-PUF60 antibodies were present in 25/84 (30%) patients with SS, 6/71 (8.5%) patients with SLE and 2/38 (5.0%) control subjects (SS vs controls, p=0.002; SLE vs controls, p=0.711). Anti-PUF60 antibodies were present in 48/267 (18.0%) patients with DM versus 4/45 (8.9%) and 5/45 (11.1%) patients with inclusion body myositis and polymyositis, respectively. The antibody was significantly associated with anti-Ro52 antibodies, rheumatoid factor and hyperglobulinemia in the patients with primary SS. In patients with DM, the antibody was associated with anti-transcription intermediary factor 1 gamma seropositivity and Caucasian race.PUF60 represents a novel autoantigen in patients with SS and DM. PUF60 antibodies are associated with distinct clinical features and different immune responses in different diseases.

  View details for DOI 10.1136/annrheumdis-2015-207509

  View details for Web of Science ID 000376440900033

  View details for PubMedID 26253095

• JAK2-positive cutaneous myelofibrosis presenting as sclerosing extramedullary hematopoietic tumors on the scalp: case presentation and review of the literature. Journal of cutaneous pathology LeBlanc, R. E., Lester, L., Kwong, B., Rieger, K. E. 2015; 42 (11): 858-862

  Abstract

  We report the second case of cutaneous myelofibrosis with a documented JAK2 activating mutation involving the scalp of a 67-year-old woman with primary myelofibrosis in her marrow. In contrast to the previous case, the biopsy revealed extensive lesional collagen deposition and closely mimicked a fibrohistiocytic proliferation. Similar rare lesions occurring in the setting of myeloproliferative neoplasms have been called sclerosing extramedullary hematopoietic tumors. These entities appear histomorphologically and etiologically distinct from extramedullary hematopoiesis, and their diagnosis should prompt the workup for a myeloproliferative neoplasm in the absence of an antecedent diagnosis. The presence of the JAK2 mutation in our case confirmed that the lesions represented skin involvement by a neoplastic myeloid proliferation and not compensatory extramedullary hematopoiesis. Our patient died of disease several months following the appearance of her lesions, which is in keeping with other reports that suggest that cutaneous myelofibrosis may serve as an independent poor prognostic sign in otherwise advanced primary myelofibrosis. A review of the literature further emphasizes the importance of distinguishing this entity from mesenchymal neoplasms and acute myeloid leukemia involving the skin.

  View details for DOI 10.1111/cup.12553

  View details for PubMedID 26153565

• JAK2-positive cutaneous myelofibrosis presenting as sclerosing extramedullary hematopoietic tumors on the scalp: case presentation and review of the literature JOURNAL OF CUTANEOUS PATHOLOGY LeBlanc, R. E., Lester, L., Kwong, B., Rieger, K. E. 2015; 42 (11): 858-862

  View details for DOI 10.1111/cup.12553

  View details for Web of Science ID 000368293300010

• A subdermal source: contact dermatitis. American journal of medicine Fogel, A. L., Longmire, M., Rieger, K. E., Sarin, K. Y. 2015; 128 (6): 578-581

  View details for DOI 10.1016/j.amjmed.2015.02.005

  View details for PubMedID 25747191

• ETV3-NCOA2 in indeterminate cell histiocytosis: clonal translocation supports sui generis. Blood Brown, R. A., Kwong, B. Y., McCalmont, T. H., Ragsdale, B., Ma, L., Cheung, C., Rieger, K. E., Arber, D. A., Kim, J. 2015

  View details for DOI 10.1182/blood-2015-07-655530

  View details for PubMedID 26438513

• Localized cutaneous fibrosing disorders. Rheumatic diseases clinics of North America Yaqub, A., Chung, L., Rieger, K. E., Fiorentino, D. F. 2013; 39 (2): 347-364

  Abstract

  This article acquaints the reader with disorders of the skin that might mimic systemic sclerosis but whose pathology is localized to the skin and/or has extracutaneous manifestations that are different than systemic sclerosis. These disorders include localized scleroderma (morphea), eosinophilic fasciitis, scleredema, scleromyxedema, nephrogenic systemic fibrosis, and chronic graft-versus-host disease. Particular emphasis is placed on clinical and histopathologic features that help the clinician differentiate between these disorders. Treatment options are briefly reviewed.

  View details for DOI 10.1016/j.rdc.2013.02.013

  View details for PubMedID 23597968

• Localized cutaneous fibrosing disorders. Rheumatic diseases clinics of North America Yaqub, A., Chung, L., Rieger, K. E., Fiorentino, D. F. 2013; 39 (2): 347-364

  View details for DOI 10.1016/j.rdc.2013.02.013

  View details for PubMedID 23597968

• Reconsidering the Diagnostic and Prognostic Utility of LN-2 for Undifferentiated Pleomorphic Sarcoma and Atypical Fibroxanthoma AMERICAN JOURNAL OF DERMATOPATHOLOGY Hollmig, S. T., Rieger, K. E., Henderson, M. T., West, R. B., Sundram, U. N. 2013; 35 (2): 176-179

  Abstract

  The topic of distinguishing atypical fibroxanthoma (AFX) from undifferentiated pleomorphic sarcoma (UPS), formerly malignant fibrous histiocytoma, is highly controversial. Although their clinical behavior is disparate, AFX and UPS commonly appear nearly identical on routine histopathologic examination. Although conceptually useful, subcategorization of UPS into superficial (confined to the dermis and subcutaneous tissue) and deep (involvement of fascia and deeper structures) types has not improved our ability to differentiate UPS from AFX. Numerous authors have purported LN-2 (CD74) immunopositivity as able to distinguish UPS from AFX and to predict those rare AFX likely to behave aggressively, although only a single prior study has been dedicated to evaluating this marker. We performed LN-2 staining of 14 AFX, 8 superficial UPS, and 65 deep UPS specimens using an identical protocol as described by prior authors. Of the 73 total UPS specimens, only 1 (1.4%) stained strongly with LN-2, as compared with 3 of 14 (21%) AFX (P = 0.012). One of 2 (50%) clinically aggressive AFX tumors that later exhibited both local recurrence and metastasis stained strongly for LN-2, whereas 2 of 12 (17%) of the more indolent tumors stained strongly with this marker (P = 0.40). Our data do not replicate prior reports of LN-2 as a sensitive and specific marker for UPS, or as indicative of prognosis for AFX, and therefore does not support the use of LN-2 as either a diagnostic or prognostic marker.

  View details for DOI 10.1097/DAD.0b013e318265fb9e

  View details for Web of Science ID 000316941200009

  View details for PubMedID 23000905

• ALK-negative systemic intravascular anaplastic large cell lymphoma presenting in the skin JOURNAL OF CUTANEOUS PATHOLOGY Rieger, K. E., POLIDORE, T., Warnke, R., Kim, J. 2011; 38 (2): 216-220

  Abstract

  Systemic cases of the CD30-positive T-cell neoplasm, anaplastic large cell lymphoma (ALCL), are typically anaplastic lymphoma kinase (ALK)-positive. The failure to express ALK protein has been shown to portend a worse prognosis. We describe a case of ALK-negative systemic ALCL that presented as a violaceous plaque on the scalp of a 79-year-old man. Interestingly, the neoplastic cells were confined largely within vascular spaces, a configuration that is exceedingly rare in the skin and is more typically seen with intravascular large B-cell lymphoma. In addition, bcl-2 immunohistochemical staining was strongly positive in this case, which may portend a more aggressive clinical course. To our knowledge, this report represents the first case of an ALK-negative ALCL to present intravascularly in the skin. Therefore, the recognition of systemic anaplastic T-cell lymphoma present within the intravascular spaces is important to avoid misdiagnosis.

  View details for DOI 10.1111/j.1600-0560.2010.01528.x

  View details for Web of Science ID 000285754200009

  View details for PubMedID 20236372

• Skin Nodules in a Patient With Acute Myeloid Leukemia and Neurological Deterioration - Disseminated fusariosis ARCHIVES OF DERMATOLOGY Rieger, K. E., Ridky, T. W., Sundram, U. N. 2010; 146 (9): 1037-1042

  View details for Web of Science ID 000282004600028

  View details for PubMedID 20855710

• Recurrence rates associated with incompletely excised low-risk nonmelanoma skin cancer JOURNAL OF CUTANEOUS PATHOLOGY Rieger, K. E., Linos, E., Egbert, B. M., Swetter, S. M. 2010; 37 (1): 59-67

  Abstract

  Reported recurrence rates for transected nonmelanoma skin cancer (NMSC) vary widely, and few studies have addressed recurrence of tumors followed clinically or treated with nonsurgical modalities.Retrospective review of dermatopathology records from January 1999 to January 2005 was conducted to identify biopsies or excision specimens with histologically transected basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) which were not subsequently excised. Patient and tumor characteristics associated with recurrence were analyzed in a subgroup of patients with predominantly 'low-risk' and/or minimally transected NMSCs. Prospective follow up was performed through March 31, 2008. Data was analyzed with Chi-square and Fishers exact tests and multivariate logistic regression.Of 376 transected NMSCs, 27 (7.2%) recurred, including 20 (9%) of 223 BCCs and 7 (4.6%) SCCs in situ of 153 SCCs. The overall recurrence rate of the 124 minimally transected NMSCs was even lower (5.6%). Multivariate logistic regression identified three significant predictors of recurrence: tumor location on the head and neck (p = 0.041), tumor size (p = 0.00741) and superficial subtype of BCC (p = .035).Although surgical excision of NMSC remains the standard of care, observation or nonsurgical treatment may be acceptable in many cases of incompletely excised low-risk or minimally transected NMSCs.

  View details for DOI 10.1111/j.1600-0560.2009.01340.x

  View details for Web of Science ID 000272165500010

  View details for PubMedID 19615009

• Toxicity from radiation therapy associated with abnormal transcriptional responses to DNA damage PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Rieger, K. E., Hong, W. J., Tusher, V. G., Tang, J., Tibshirani, R., Chu, G. 2004; 101 (17): 6635-6640

  Abstract

  Toxicity from radiation therapy is a grave problem for cancer patients. We hypothesized that some cases of toxicity are associated with abnormal transcriptional responses to radiation. We used microarrays to measure responses to ionizing and UV radiation in lymphoblastoid cells derived from 14 patients with acute radiation toxicity. The analysis used heterogeneity-associated transformation of the data to account for a clinical outcome arising from more than one underlying cause. To compute the risk of toxicity for each patient, we applied nearest shrunken centroids, a method that identifies and cross-validates predictive genes. Transcriptional responses in 24 genes predicted radiation toxicity in 9 of 14 patients with no false positives among 43 controls (P = 2.2 x 10(-7)). The responses of these nine patients displayed significant heterogeneity. Of the five patients with toxicity and normal responses, two were treated with protocols that proved to be highly toxic. These results may enable physicians to predict toxicity and tailor treatment for individual patients.

  View details for DOI 10.1073/pnas.0307761101

  View details for Web of Science ID 000221107900056

  View details for PubMedID 15096622

  View details for PubMedCentralID PMC404097

• Portrait of transcriptional responses to ultraviolet and ionizing radiation in human cells NUCLEIC ACIDS RESEARCH Rieger, K. E., Chu, G. 2004; 32 (16): 4786-4803

  Abstract

  To understand the human response to DNA damage, we used microarrays to measure transcriptional responses of 10 000 genes to ionizing radiation (IR) and ultraviolet radiation (UV). To identify bona fide responses, we used cell lines from 15 individuals and a rigorous statistical method, Significance Analysis of Microarrays (SAM). By exploring how sample number affects SAM, we rendered a portrait of the human damage response with a degree of accuracy unmatched by previous studies. By showing how SAM can be used to estimate the total number of responsive genes, we discovered that 24% of all genes respond to IR and 32% respond to UV, although most responses were less than 2-fold. Many genes were involved in known damage-response pathways for cell cycling and proliferation, apoptosis, DNA repair or the stress response. However, the majority of genes were involved in unexpected pathways, with functions in signal transduction, RNA binding and editing, protein synthesis and degradation, energy metabolism, metabolism of macromolecular precursors, cell structure and adhesion, vesicle transport, or lysosomal metabolism. Although these functions were not previously associated with the damage response in mammals, many were conserved in yeast. These insights reveal new directions for studying the human response to DNA damage.

  View details for DOI 10.1093/nar/gkh783

  View details for Web of Science ID 000224207500009

  View details for PubMedID 15356296

  View details for PubMedCentralID PMC519099