Sunhee S. Kim, MD

All Publications

• Sex-Biased ZRSR2 Mutations in Myeloid Malignancies Impair Plasmacytoid Dendritic Cell Activation and Apoptosis. Cancer discovery Togami, K., Chung, S. S., Madan, V., Booth, C. A., Kenyon, C. M., Cabal-Hierro, L., Taylor, J., Kim, S. S., Griffin, G. K., Ghandi, M., Li, J., Li, Y. Y., Angelot-Delettre, F., Biichle, S., Seiler, M., Buonamici, S., Lovitch, S. B., Louissaint, A., Morgan, E. A., Jardin, F., Piccaluga, P. P., Weinstock, D. M., Hammerman, P. S., Yang, H., Konopleva, M., Pemmaraju, N., Garnache-Ottou, F., Abdel-Wahab, O., Koeffler, H. P., Lane, A. A. 2022; 12 (2): 522-541

  Abstract

  Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive leukemia of plasmacytoid dendritic cells (pDC). BPDCN occurs at least three times more frequently in men than in women, but the reasons for this sex bias are unknown. Here, studying genomics of primary BPDCN and modeling disease-associated mutations, we link acquired alterations in RNA splicing to abnormal pDC development and inflammatory response through Toll-like receptors. Loss-of-function mutations in ZRSR2, an X chromosome gene encoding a splicing factor, are enriched in BPDCN, and nearly all mutations occur in males. ZRSR2 mutation impairs pDC activation and apoptosis after inflammatory stimuli, associated with intron retention and inability to upregulate the transcription factor IRF7. In vivo, BPDCN-associated mutations promote pDC expansion and signatures of decreased activation. These data support a model in which male-biased mutations in hematopoietic progenitors alter pDC function and confer protection from apoptosis, which may impair immunity and predispose to leukemic transformation. SIGNIFICANCE: Sex bias in cancer is well recognized, but the underlying mechanisms are incompletely defined. We connect X chromosome mutations in ZRSR2 to an extremely male-predominant leukemia. Aberrant RNA splicing induced by ZRSR2 mutation impairs dendritic cell inflammatory signaling, interferon production, and apoptosis, revealing a sex- and lineage-related tumor suppressor pathway.This article is highlighted in the In This Issue feature, p. 275.

  View details for DOI 10.1158/2159-8290.CD-20-1513

  View details for PubMedID 34615655

  View details for PubMedCentralID PMC8831459

• Laparoscopic pancreatectomy for cancer in high volume centers is associated with an increased use and fewer delays of adjuvant chemotherapy. HPB : the official journal of the International Hepato Pancreato Biliary Association Kutlu, O. C., Vega, E. A., Salehi, O., Lathan, C., Kim, S., Krishnan, S., Stallwood, C., Kozyreva, O., Conrad, C. 2021; 23 (4): 625-632

  Abstract

  This study aimed to investigate the relationship between hospital case volume, surgical approach and AC-use in patients who underwent pancreatectomy for pancreatic ductal adenocarcinoma (PDAC).Patients were divided into quartiles by institutional pancreatectomy case volume, resection type (pancreaticoduodenectomy [PD], distal pancreatectomy [DP], or total pancreatectomy [TP]) and surgical approach (laparoscopic vs. open). The rates and contributing factors of AC administration and delay >90 days were compared among volume quartiles and surgical approaches.This study identified 23,494 patients who had undergone pancreatectomy for PDAC between 2010 and 2016 and met inclusion criteria. After correcting for confounders, compared to low volume hospitals patients at high-case-volume hospitals had the highest rates of AC administration after PD and DP. Moreover, compared to open surgery for all resection types, laparoscopic surgery was associated with a higher rate of AC use at high and highest-case-volume hospitals and less delay to chemotherapy at high-volume hospitals. For DP, laparoscopic approach had a positive impact on AC delay >90-day at the highest volume institutions only.Laparoscopic surgery for pancreatic cancer leads to higher utilization and lower probability of delay of AC in high and highest volume hospitals.

  View details for DOI 10.1016/j.hpb.2020.09.003

  View details for PubMedID 32988752

• Neoadjuvant FOLFIRINOX in Patients With Borderline Resectable Pancreatic Cancer: A Systematic Review and Patient-Level Meta-Analysis. Journal of the National Cancer Institute Janssen, Q. P., Buettner, S., Suker, M., Beumer, B. R., Addeo, P., Bachellier, P., Bahary, N., Bekaii-Saab, T., Bali, M. A., Besselink, M. G., Boone, B. A., Chau, I., Clarke, S., Dillhoff, M., El-Rayes, B. F., Frakes, J. M., Grose, D., Hosein, P. J., Jamieson, N. B., Javed, A. A., Khan, K., Kim, K. P., Kim, S. C., Kim, S. S., Ko, A. H., Lacy, J., Margonis, G. A., McCarter, M. D., McKay, C. J., Mellon, E. A., Moorcraft, S. Y., Okada, K. I., Paniccia, A., Parikh, P. J., Peters, N. A., Rabl, H., Samra, J., Tinchon, C., van Tienhoven, G., van Veldhuisen, E., Wang-Gillam, A., Weiss, M. J., Wilmink, J. W., Yamaue, H., Homs, M. Y., van Eijck, C. H., Katz, M. H., Groot Koerkamp, B. 2019; 111 (8): 782-794

  Abstract

  FOLFIRINOX is a standard treatment for metastatic pancreatic cancer patients. The effectiveness of neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer (BRPC) remains debated.We performed a systematic review and patient-level meta-analysis on neoadjuvant FOLFIRINOX in patients with BRPC. Studies with BRPC patients who received FOLFIRINOX as first-line neoadjuvant treatment were included. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival, resection rate, R0 resection rate, and grade III-IV adverse events. Patient-level survival outcomes were obtained from authors of the included studies and analyzed using the Kaplan-Meier method.We included 24 studies (8 prospective, 16 retrospective), comprising 313 (38.1%) BRPC patients treated with FOLFIRINOX. Most studies (n = 20) presented intention-to-treat results. The median number of administered neoadjuvant FOLFIRINOX cycles ranged from 4 to 9. The resection rate was 67.8% (95% confidence interval [CI] = 60.1% to 74.6%), and the R0-resection rate was 83.9% (95% CI = 76.8% to 89.1%). The median OS varied from 11.0 to 34.2 months across studies. Patient-level survival data were obtained for 20 studies representing 283 BRPC patients. The patient-level median OS was 22.2 months (95% CI = 18.8 to 25.6 months), and patient-level median progression-free survival was 18.0 months (95% CI = 14.5 to 21.5 months). Pooled event rates for grade III-IV adverse events were highest for neutropenia (17.5 per 100 patients, 95% CI = 10.3% to 28.3%), diarrhea (11.1 per 100 patients, 95% CI = 8.6 to 14.3), and fatigue (10.8 per 100 patients, 95% CI = 8.1 to 14.2). No deaths were attributed to FOLFIRINOX.This patient-level meta-analysis of BRPC patients treated with neoadjuvant FOLFIRINOX showed a favorable median OS, resection rate, and R0-resection rate. These results need to be assessed in a randomized trial.

  View details for DOI 10.1093/jnci/djz073

  View details for PubMedID 31086963

  View details for PubMedCentralID PMC6695305

• Comparison of Tumor Regression Grading of Residual Pancreatic Ductal Adenocarcinoma Following Neoadjuvant Chemotherapy Without Radiation: Would Fewer Tier-Stratification Be Favorable Toward Standardization? The American journal of surgical pathology Kim, S. S., Ko, A. H., Nakakura, E. K., Wang, Z. J., Corvera, C. U., Harris, H. W., Kirkwood, K. S., Hirose, R., Tempero, M. A., Kim, G. E. 2019; 43 (3): 334-340

  Abstract

  To assess whether the College of American Pathologists (CAP) and the Evans grading systems for neoadjuvant chemotherapy without radiation-treated pancreatectomy specimens are prognostic, and if a 3-tier stratification scheme preserves data granularity. Conducted retrospective review of 32 patients with ordinary pancreatic ductal adenocarcinoma treated with neoadjuvant therapy without radiation followed by surgical resection. Final pathologic tumor category (AJCC eighth edition) was 46.9% ypT1, 34.4% ypT2, and 18.7% ypT3. Median follow-up time was 29.8 months, median disease-free survival (DFS) was 19.6 months, and median overall survival (OS) was 34.2 months. CAP score 1, 2, 3 were present in 5 (15.6%), 18 (56.3%), and 9 (28.1%) patients, respectively. Evans grade III, IIb, IIa, and I were present in 10 (31.2%), 8 (25.0%), 7 (21.9%), and 7 (21.9%) patients, respectively. OS (CAP: P=0.005; Evans: P=0.001) and DFS (CAP: P=0.003; Evans: P=0.04) were statistically significant for both CAP and Evans. Stratified CAP scores 1 and 2 versus CAP score 3 was statistically significant for both OS (P=0.002) and DFS (P=0.002). Stratified Evans grades I, IIa, and IIb versus Evans grade III was statistically significant for both OS (P=0.04) and DFS (P=0.02). CAP, Evans, and 3-tier stratification are prognostic of OS and DFS.

  View details for DOI 10.1097/PAS.0000000000001152

  View details for PubMedID 30211728

• Undifferentiated pleomorphic sarcoma: Factors predictive of adverse outcomes. Journal of the American Academy of Dermatology Winchester, D., Lehman, J., Tello, T., Chimato, N., Hocker, T., Kim, S., Chang, J., Markey, J., Yom, S. S., Ryan, W., Mully, T., Hodge, D., Otley, C., Arron, S. T. 2018; 79 (5): 853-859

  Abstract

  Undifferentiated pleomorphic sarcoma (UPS) encompasses rare neoplasms that can arise either in the dermis or in the subfascial soft tissue. The behavior of UPS ranges from indolent to aggressive, but data predicting outcomes are limited.Identify predictors of poor outcomes by analyzing a large collection of UPS cases.We evaluated all available cases of UPS (including those termed atypical fibroxanthoma, malignant fibrous histiocytoma, pleomorphic dermal sarcoma, and subfascial UPS) across 3 tertiary care centers.Among the 319 patients, 45 experienced recurrence, 33 experienced metastasis, and 96 died of any cause. Risk factors for recurrence were clinical tumor size larger than 5 cm and invasion beyond subcutaneous fat. Risk factors for distant metastases were tumor site, tumor size larger than 2 cm, invasion beyond subcutaneous fat, and lymphovascular invasion. Risk factors for overall mortality were age, immunosuppression, tumor size larger than 2 cm, and lymphovascular invasion. History of skin cancer was associated with a lower risk of recurrence and metastasis.This was a retrospective study.Using the unbiased approach of pooling all UPS cases regardless of terminology, we identified clinical and histologic factors predicting poor outcomes. We propose subcategorization of UPS (into superficial versus deep UPS), which is consistent with the American Joint Committee on Cancer staging of soft-tissue sarcoma.

  View details for DOI 10.1016/j.jaad.2018.05.022

  View details for PubMedID 29787841

• Parp3 promotes long-range end joining in murine cells PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Layer, J., Cleary, J., Brown, A. J., Stevenson, K. E., Morrow, S. N., Van Scoyk, A., Blasco, R. B., Karaca, E., Meng, F., Frock, R. L., Tivey, T., Kim, S., Fuchs, H., Chiarle, R., Alt, F. W., Roberts, S. A., Weinstock, D. M., Day, T. A. 2018; 115 (40): 10076–81

  Abstract

  Chromosomal rearrangements, including translocations, are early and essential events in the formation of many tumors. Previous studies that defined the genetic requirements for rearrangement formation have identified differences between murine and human cells, most notably in the role of classic and alternative nonhomologous end-joining (NHEJ) factors. We reported that poly(ADP)ribose polymerase 3 (PARP3) promotes chromosomal rearrangements induced by endonucleases in multiple human cell types. We show here that in contrast to classic (c-NHEJ) factors, Parp3 also promotes rearrangements in murine cells, including translocations in murine embryonic stem cells (mESCs), class-switch recombination in primary B cells, and inversions in tail fibroblasts that generate Eml4-Alk fusions. In mESCs, Parp3-deficient cells had shorter deletion lengths at translocation junctions. This was corroborated using next-generation sequencing of Eml4-Alk junctions in tail fibroblasts and is consistent with a role for Parp3 in promoting the processing of DNA double-strand breaks. We confirmed a previous report that Parp1 also promotes rearrangement formation. In contrast with Parp3, rearrangement junctions in the absence of Parp1 had longer deletion lengths, suggesting that Parp1 may suppress double-strand break processing. Together, these data indicate that Parp3 and Parp1 promote rearrangements with distinct phenotypes.

  View details for DOI 10.1073/pnas.1801591115

  View details for Web of Science ID 000446078700075

  View details for PubMedID 30213852

  View details for PubMedCentralID PMC6176633

• PARP3 is a promoter of chromosomal rearrangements and limits G4 DNA. Nature communications Day, T. A., Layer, J. V., Cleary, J. P., Guha, S., Stevenson, K. E., Tivey, T., Kim, S., Schinzel, A. C., Izzo, F., Doench, J., Root, D. E., Hahn, W. C., Price, B. D., Weinstock, D. M. 2017; 8: 15110

  Abstract

  Chromosomal rearrangements are essential events in the pathogenesis of both malignant and nonmalignant disorders, yet the factors affecting their formation are incompletely understood. Here we develop a zinc-finger nuclease translocation reporter and screen for factors that modulate rearrangements in human cells. We identify UBC9 and RAD50 as suppressors and 53BP1, DDB1 and poly(ADP)ribose polymerase 3 (PARP3) as promoters of chromosomal rearrangements across human cell types. We focus on PARP3 as it is dispensable for murine viability and has druggable catalytic activity. We find that PARP3 regulates G quadruplex (G4) DNA in response to DNA damage, which suppresses repair by nonhomologous end-joining and homologous recombination. Chemical stabilization of G4 DNA in PARP3-/- cells leads to widespread DNA double-strand breaks and synthetic lethality. We propose a model in which PARP3 suppresses G4 DNA and facilitates DNA repair by multiple pathways.

  View details for DOI 10.1038/ncomms15110

  View details for PubMedID 28447610

  View details for PubMedCentralID PMC5414184

• A Patient with HIV-Associated Metastatic Anal Squamous Cell Carcinoma Receiving Multimodality Therapy with Curative Intent: Case Report and Review of the Literature. Journal of gastrointestinal cancer Kim, S. S., Kim, G. E., Ko, A. H. 2017; 48 (1): 94-99

  View details for DOI 10.1007/s12029-016-9814-8

  View details for PubMedID 26961789

• Preoperative FOLFIRINOX for borderline resectable pancreatic cancer: Is radiation necessary in the modern era of chemotherapy? Journal of surgical oncology Kim, S. S., Nakakura, E. K., Wang, Z. J., Kim, G. E., Corvera, C. U., Harris, H. W., Kirkwood, K. S., Hirose, R., Tempero, M. A., Ko, A. H. 2016; 114 (5): 587-596

  Abstract

  No consensus exists regarding the optimal neoadjuvant treatment paradigm for patients with borderline resectable pancreatic cancer (BRPC), including the respective roles of chemotherapy and radiation.We performed a retrospective analysis, including detailed pathologic and radiologic review, of pancreatic cancer patients undergoing FOLFIRINOX, with or without radiation therapy (RT), prior to surgical resection at a high-volume academic center over a 4-year period.Of 26 patients meeting inclusion criteria, 22 (84.6%) received FOLFIRINOX alone without RT (median number of treatment cycles = 9). The majority of patients met formal radiographic criteria for BRPC, with the superior mesenteric vein representing the most common vessel involved. R0 resection rate was 90.9%, with 12 patients (54.5%) requiring vascular reconstruction. Treatment response was classified as moderate or marked in 16 patients (72.7%) according to the College of American Pathologists grading system. Estimated median disease-free and overall survival rates are 22.6 months and not reached (NR), respectively.This is one of the largest series to describe the use of neoadjuvant FOLFIRINOX, without radiation therapy, in patients with BRPC undergoing surgical resection. Given the high R0 resection rates and favorable clinical outcomes with chemotherapy alone, this strategy should be further assessed in prospective study design. J. Surg. Oncol. 2016;114:587-596. © 2016 Wiley Periodicals, Inc.

  View details for DOI 10.1002/jso.24375

  View details for PubMedID 27444658

• Pediatric-type nodal follicular lymphoma: a biologically distinct lymphoma with frequent MAPK pathway mutations. Blood Louissaint, A., Schafernak, K. T., Geyer, J. T., Kovach, A. E., Ghandi, M., Gratzinger, D., Roth, C. G., Paxton, C. N., Kim, S., Namgyal, C., Morin, R., Morgan, E. A., Neuberg, D. S., South, S. T., Harris, M. H., Hasserjian, R. P., Hochberg, E. P., Garraway, L. A., Harris, N. L., Weinstock, D. M. 2016; 128 (8): 1093-1100

  Abstract

  Pediatric-type nodal follicular lymphoma (PTNFL) is a variant of follicular lymphoma (FL) characterized by limited-stage presentation and invariably benign behavior despite often high-grade histological appearance. It is important to distinguish PTNFL from typical FL in order to avoid unnecessary treatment; however, this distinction relies solely on clinical and pathological criteria, which may be variably applied. To define the genetic landscape of PTNFL, we performed copy-number analysis, exome and/or targeted sequencing of 26 PTNFLs (16 pediatric, 10 adult). The most commonly mutated gene in PTNFL was MAP2K1, encoding MEK1, with a mutation frequency of 43%. All MAP2K1 mutations were activating missense mutations localized to exons 2 and 3, which encode negative regulatory and catalytic domains, respectively. Missense mutations in MAPK1 (2/22), and RRAS (1/22) were identified in cases that lacked MAP2K1 mutations. The second most commonly mutated gene in PTNFL was TNFRSF14, with a mutation frequency of 29%, similar to that seen in limited-stage typical FL (p=0.35). PTNFL was otherwise genomically bland, and specifically lacked recurrent mutations in epigenetic modifiers (e.g. CREBBP, KMT2D). Copy number aberrations (CNAs) affected a mean of only 0.5% of PTNFL genomes, compared to 10% of limited-stage typical FL genomes (p<0.02). Importantly, the mutational profiles of PTNFLs in children and adults were highly similar. Together, these findings define PTNFL as a biologically and clinically distinct indolent lymphoma of children and adults characterized by a high prevalence of MAP kinase pathway mutations and a near absence of mutations in epigenetic modifiers.

  View details for DOI 10.1182/blood-2015-12-682591

  View details for PubMedID 27325104

• Pediatric-Type Nodal Follicular Lymphoma in Children and Adults Is Nearly Genetically Silent and Biologically Distinct from Typical Follicular Lymphoma Louissaint, A., Schafernak, K. T., Geyer, J. T., Kovach, A. E., Gratzinger, D., Roth, C. G., Paxton, C. N., Kim, S., Namgyal, C., Morgan, E. A., South, S. T., Harris, M. H., Hochberg, E. P., Hasserjian, R. P., Harris, N. L., Weinstock, D. M. AMER SOC HEMATOLOGY. 2015

  View details for Web of Science ID 000368021800182

• Mutations in G protein beta subunits promote transformation and kinase inhibitor resistance NATURE MEDICINE Yoda, A., Adelmant, G., Tamburini, J., Chapuy, B., Shindoh, N., Yoda, Y., Weigert, O., Kopp, N., Wu, S., Kim, S. S., Liu, H., Tivey, T., Christie, A. L., Elpek, K. G., Card, J., Gritsman, K., Gotlib, J., Deininger, M. W., Makishima, H., Turley, S. J., Javidi-Sharifi, N., Maciejewski, J. P., Jaiswal, S., Ebert, B. L., Rodig, S. J., Tyner, J. W., Marto, J. A., Weinstock, D. M., Lane, A. A. 2015; 21 (1): 71-75

  Abstract

  Activating mutations in genes encoding G protein α (Gα) subunits occur in 4-5% of all human cancers, but oncogenic alterations in Gβ subunits have not been defined. Here we demonstrate that recurrent mutations in the Gβ proteins GNB1 and GNB2 confer cytokine-independent growth and activate canonical G protein signaling. Multiple mutations in GNB1 affect the protein interface that binds Gα subunits as well as downstream effectors and disrupt Gα interactions with the Gβγ dimer. Different mutations in Gβ proteins clustered partly on the basis of lineage; for example, all 11 GNB1 K57 mutations were in myeloid neoplasms, and seven of eight GNB1 I80 mutations were in B cell neoplasms. Expression of patient-derived GNB1 variants in Cdkn2a-deficient mouse bone marrow followed by transplantation resulted in either myeloid or B cell malignancies. In vivo treatment with the dual PI3K-mTOR inhibitor BEZ235 suppressed GNB1-induced signaling and markedly increased survival. In several human tumors, mutations in the gene encoding GNB1 co-occurred with oncogenic kinase alterations, including the BCR-ABL fusion protein, the V617F substitution in JAK2 and the V600K substitution in BRAF. Coexpression of patient-derived GNB1 variants with these mutant kinases resulted in inhibitor resistance in each context. Thus, GNB1 and GNB2 alterations confer transformed and resistance phenotypes across a range of human tumors and may be targetable with inhibitors of G protein signaling.

  View details for DOI 10.1038/nm.3751

  View details for PubMedID 25485910

• GNB1 Activating Mutations Promote Myeloid and Lymphoid Neoplasms Targetable By Combined PI3K/mTOR Inhibition Yoda, A., Adelmant, G., Tamburini, J., Chapuy, B., Shindoh, N., Yoda, Y., Weigert, O., Kopp, N., Wu, S., Kim, S. S., Liu, H., Tivey, T., Christie, A. L., Elpek, K. G., Card, J., Gritsman, K., Gotlib, J., Deininger, M. W., Makishima, H., Turley, S., Javidi-Sharifi, N., Maciejewski, J. P., Rodig, S. J., Tyner, J. W., Marto, J. A., Weinstock, D. M., Lane, A. A. AMER SOC HEMATOLOGY. 2014

  View details for Web of Science ID 000349242702149

• Characterization of the roles of Blt1p in fission yeast cytokinesis. Molecular biology of the cell Goss, J. W., Kim, S., Bledsoe, H., Pollard, T. D. 2014; 25 (13): 1946-57

  Abstract

  Spatial and temporal regulation of cytokinesis is essential for cell division, yet the mechanisms that control the formation and constriction of the contractile ring are incompletely understood. In the fission yeast Schizosaccharomyces pombe proteins that contribute to the cytokinetic contractile ring accumulate during interphase in nodes-precursor structures around the equatorial cortex. During mitosis, additional proteins join these nodes, which condense to form the contractile ring. The cytokinesis protein Blt1p is unique in being present continuously in nodes from early interphase through to the contractile ring until cell separation. Blt1p was shown to stabilize interphase nodes, but its functions later in mitosis were unclear. We use analytical ultracentrifugation to show that purified Blt1p is a tetramer. We find that Blt1p interacts physically with Sid2p and Mob1p, a protein kinase complex of the septation initiation network, and confirm known interactions with F-BAR protein Cdc15p. Contractile rings assemble normally in blt1∆ cells, but the initiation of ring constriction and completion of cell division are delayed. We find three defects that likely contribute to this delay. Without Blt1p, contractile rings recruited and retained less Sid2p/Mob1p and Clp1p phosphatase, and β-glucan synthase Bgs1p accumulated slowly at the cleavage site.

  View details for DOI 10.1091/mbc.E13-06-0300

  View details for PubMedID 24790095

  View details for PubMedCentralID PMC4072569

• A targeted mutational landscape of angioimmunoblastic T-cell lymphoma. Blood Odejide, O., Weigert, O., Lane, A. A., Toscano, D., Lunning, M. A., Kopp, N., Kim, S., van Bodegom, D., Bolla, S., Schatz, J. H., Teruya-Feldstein, J., Hochberg, E., Louissaint, A., Dorfman, D., Stevenson, K., Rodig, S. J., Piccaluga, P. P., Jacobsen, E., Pileri, S. A., Harris, N. L., Ferrero, S., Inghirami, G., Horwitz, S. M., Weinstock, D. M. 2014; 123 (9): 1293-6

  Abstract

  The genetics of angioimmunoblastic T-cell lymphoma (AITL) are very poorly understood. We defined the mutational landscape of AITL across 219 genes in 85 cases from the United States and Europe. We identified ≥2 mutations in 34 genes, nearly all of which were not previously implicated in AITL. These included loss-of-function mutations in TP53 (n = 4), ETV6 (n = 3), CCND3 (n = 2), and EP300 (n = 5), as well as gain-of-function mutations in JAK2 (n = 2) and STAT3 (n = 4). TET2 was mutated in 65 (76%) AITLs, including 43 that harbored 2 or 3 TET2 mutations. DNMT3A mutations occurred in 28 (33%) AITLs; 100% of these also harbored TET2 mutations (P < .0001). Seventeen AITLs harbored IDH2 R172 substitutions, including 15 with TET2 mutations. In summary, AITL is characterized by high frequencies of overlapping mutations in epigenetic modifiers and targetable mutations in a subset of cases.

  View details for DOI 10.1182/blood-2013-10-531509

  View details for PubMedID 24345752

  View details for PubMedCentralID PMC4260974

• Low frequency clonal mutations recoverable by deep sequencing in patients with aplastic anemia. Leukemia Lane, A. A., Odejide, O., Kopp, N., Kim, S., Yoda, A., Erlich, R., Wagle, N., Abel, G. A., Rodig, S. J., Antin, J. H., Weinstock, D. M. 2013; 27 (4): 968-71

  View details for DOI 10.1038/leu.2013.30

  View details for PubMedID 23370706

  View details for PubMedCentralID PMC4552245