The Genetic Basis of Hepatosplenic T-cell Lymphoma

McKinney, Matthew; Moffitt, Andrea; Gaulard, Philippe; Travert, Marion; Leval, Laurence de; Nicolae, Alina; Raffeld, Mark; Jaffe, Elaine S.; Pittaluga, Stefania; Xi, Liqiang; Heavican, Tayla B.; Iqbal, Javeed; Belhadj, Karim; Delfau‐Larue, M.‐H.; Fataccioli, Virginie; Czader, Magdalena; Lossos, Izidore S.; Chapman-Fredricks, Jennifer R.; Richards, Kristy L.; Fedoriw, Yuri; Ondrejka, Sarah L.; Hsi, Eric D.; Low, Lawrence K.; Weisenburger, Dennis D.; Chan, Wing C.; Mehta‐Shah, Neha; Horwitz, Steven M.; Bernal‐Mizrachi, Leon; Flowers, Christopher R.; Beaven, Anne; Parihar, Mayur; Baseggio, Lucile; Parrens, Marie; Moreau, Anne; Sujobert, Pierre; Pilichowska, Monika; Evens, Andrew M.; Chadburn, Amy; Au-Yeung, Rex; Srivastava, Gopesh; Choi, William W.L.; Goodlad, John R.; Aurer, Igor; Bašić-Kinda, Sandra; Gascoyne, Randy D.; Davis, Nicholas S.; Li, Guojie; Zhang, Jenny; Rajagopalan, Deepthi; Reddy, Anupama; Love, Cassandra; Levy, Shawn; Zhuang, Yuan; Datta, Jyotishka; Dunson, David B.; Davé, Sandeep S.

doi:10.1158/2159-8290.cd-16-0330

Cited by 164 publications

(141 citation statements)

References 47 publications

Supporting

Mentioning

131

Contrasting

Unclassified

Order By: Relevance

“…158 The related STAT5B is mutated far less in LGL, but more commonly in T-cell prolymphocytic leukemia 159 and enteropathy-associated T-cell lymphoma, type II (renamed as monomorphic epitheliotropic intestinal T-cell lymphoma [MEITL] in the 2016 WHO revision). [160][161][162] Both STAT3 and STAT5B are also mutated in gd-hepatosplenic/cutaneous T-cell lymphoma and nasal-type NK-/ T-cell lymphoma 160,163,164 (Table 4). SETD2 mutations were recently identified in up to 90% of MEITL and 25% of gd-hepatosplenic T-cell lymphoma.…”

Section: Mature T/nk Neoplasmsmentioning

confidence: 99%

“…SETD2 mutations were recently identified in up to 90% of MEITL and 25% of gd-hepatosplenic T-cell lymphoma. 162,165 In addition to mutations affecting the JAK-STAT pathway and epigenetic modifiers, recurrent mutations targeting the T-cell receptor signaling pathway are also frequently observed in many types of T-cell lymphomas including adult T-cell leukemia/lymphoma, PTCL, and cutaneous T-cell lymphomas (mycosis fungoides and Sézary syndrome).…”

Section: Mature T/nk Neoplasmsmentioning

confidence: 99%

See 1 more Smart Citation

Diagnosis and classification of hematologic malignancies on the basis of genetics

Taylor¹,

Xiao²,

Abdel-Wahab

2017

Blood

178

142

View full text Add to dashboard Cite

Genomic analysis has greatly influenced the diagnosis and clinical management of patients affected by diverse forms of hematologic malignancies. Here, we review how genetic alterations define subclasses of patients with acute leukemias, myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPNs), non-Hodgkin lymphomas, and classical Hodgkin lymphoma. These include new subtypes of acute myeloid leukemia defined by mutations in RUNX1 or BCR-ABL1 translocations as well as a constellation of somatic structural DNA alterations in acute lymphoblastic leukemia. Among patients with MDS, detection of mutations in SF3B1 define a subgroup of patients with the ring sideroblast form of MDS and a favorable prognosis. For patients with MPNs, detection of the BCR-ABL1 fusion delineates chronic myeloid leukemia from classic BCR-ABL1− MPNs, which are largely defined by mutations in JAK2, CALR, or MPL. In the B-cell lymphomas, detection of characteristic rearrangements involving MYC in Burkitt lymphoma, BCL2 in follicular lymphoma, and MYC/BCL2/BCL6 in high-grade B-cell lymphomas are essential for diagnosis. In T-cell lymphomas, anaplastic large-cell lymphoma is defined by mutually exclusive rearrangements of ALK, DUSP22/IRF4, and TP63. Genetic alterations affecting TP53 and the mutational status of the immunoglobulin heavy-chain variable region are important in clinical management of chronic lymphocytic leukemia. Additionally, detection of BRAFV600E mutations is helpful in the diagnosis of classical hairy cell leukemia and a number of histiocytic neoplasms. Numerous additional examples provided here demonstrate how clinical evaluation of genomic alterations have refined classification of myeloid neoplasms and major forms of lymphomas arising from B, T, or natural killer cells.

show abstract

Section: Mature T/nk Neoplasmsmentioning

confidence: 99%

Section: Mature T/nk Neoplasmsmentioning

confidence: 99%

Diagnosis and classification of hematologic malignancies on the basis of genetics

Taylor¹,

Xiao²,

Abdel-Wahab

2017

Blood

178

142

View full text Add to dashboard Cite

show abstract

“…Most subtypes are extremely rare, which has limited efforts to understand their biology and develop targeted therapeutic approaches. In this issue of Cancer Discovery , McKinney and colleagues (2) report the genetic landscape of a poor prognostic subtype of T-cell lymphoma called hepatosplenic T-cell lymphoma (HSTL). The authors collected 68 HSTL specimens from 24 institutes in 8 countries on 3 continents, a gargantuan task of cat-herding that should be enthusiastically commended.…”

mentioning

confidence: 99%

“…McKinney and colleagues (2) first performed whole exome sequencing (WES) on a discovery set of 20 HSTLs as well as paired bone marrow cells, with the latter used as “germline” comparators. WES was then performed on the 48 HSTLs that lacked bone marrow comparators, but only genes that were found to be somatically mutated in the discovery set were considered in the other 48 tumors.…”

mentioning

confidence: 99%

See 1 more Smart Citation

It Takes a Village to Unmask HSTL

Yoshida

Weinstock

2017

Cancer Discovery

View full text Add to dashboard Cite

show abstract

Association of the POT1 Germline Missense Variant p.I78T With Familial Melanoma

et al. 2019

View full text Add to dashboard Cite

The protection of telomeres 1 protein (POT1) is a critical component of the shelterin complex, a multiple-protein machine that regulates telomere length and protects telomere ends. Germline variants in POT1 have been linked to familial melanoma, and somatic mutations are associated with a range of cancers including cutaneous T-cell lymphoma (CTCL). OBJECTIVE To characterize pathogenic variation in POT1 in families with melanoma to inform clinical management. DESIGN, SETTING, AND PARTICIPANTS In this case study and pedigree evaluation, analysis of the pedigree of 1 patient with melanoma revealed a novel germline POT1 variant (p.I78T, c.233T>C, chromosome 7, g.124870933A>G, GRCh38) that was subsequently found in 2 other pedigrees obtained from the GenoMEL Consortium. MAIN OUTCOMES AND MEASURES (1) Identification of the POT1 p.I78T variant; (2) evaluation of the clinical features and characteristics of patients with this variant; (3) analysis of 3 pedigrees; (4) genomewide single-nucleotide polymorphism genotyping of germline DNA; and (5) a somatic genetic analysis of available nevi and 1 melanoma lesion. RESULTS The POT1 p.I78T variant was found in 3 melanoma pedigrees, all of persons who self-reported as being of Jewish descent, and was shown to disrupt POT1-telomere binding. A UV mutation signature was associated with nevus and melanoma formation in POT1 variant carriers, and somatic mutations in driver genes such as BRAF, NRAS, and KIT were associated with lesion development in these patients. CONCLUSIONS AND RELEVANCE POT1 p.I78T is a newly identified, likely pathogenic, variant meriting screening for in families with melanoma after more common predisposition genes such as CDKN2A have been excluded. It could also be included as part of gene panel testing.

show abstract

The Genetic Basis of Hepatosplenic T-cell Lymphoma

Cited by 164 publications

References 47 publications

Diagnosis and classification of hematologic malignancies on the basis of genetics

Diagnosis and classification of hematologic malignancies on the basis of genetics

It Takes a Village to Unmask HSTL

Association of the POT1 Germline Missense Variant p.I78T With Familial Melanoma

Contact Info

Product

Resources

About