Spectrum of hematological malignancies, clonal evolution and outcomes in 144 Mayo Clinic patients with germline predisposition syndromes

被引：26

作者：

St Martin, Emma ^{[1
]}

Ferrer, Alejandro ^{[2
]}

Mangaonkar, Abhishek A. ^{[3
]}

Khan, Shakila P. ^{[4
]}

Kohorst, Mira A. ^{[4
]}

Joshi, Avni Y. ^{[5
]}

Hogan, William J. ^{[3
]}

Olteanu, Horatiu ^{[6
]}

Moyer, Ann M. ^{[7
]}

Al-Kali, Aref ^{[3
]}

Tefferi, Ayalew ^{[3
]}

Chen, Dong ^{[6
]}

Wudhikarn, Kitsada ^{[3
]}

Go, Ronald ^{[3
]}

Viswanatha, David ^{[6
]}

He, Rong ^{[6
]}

Ketterling, Rhett ^{[6
]}

Nguyen, Phuong L. ^{[6
]}

Oliveira, Jennifer L. ^{[6
]}

Gangat, Naseema ^{[3
]}

Lasho, Terra ^{[3
]}

Patnaik, Mrinal M. ^{[3
]}

机构：

[1] Mayo Clin, Alix Sch Med, Rochester, MN 55905 USA

[2] Mayo Clin, Ctr Individualized Med, Quantitat Hlth Sci, Rochester, MN 55905 USA

[3] Mayo Clin, Div Hematol, 200 First St SW, Rochester, MN 55905 USA

[4] Mayo Clin, Div Pediat Hematol & Oncol, Rochester, MN 55905 USA

[5] Mayo Clin, Div Pediat Allergy & Immunol, Rochester, MN 55905 USA

[6] Mayo Clin, Dept Pathol, Rochester, MN 55905 USA

[7] Mayo Clin, Dept Lab Genet & Genom, Rochester, MN 55905 USA

来源：

AMERICAN JOURNAL OF HEMATOLOGY | 2021年 / 96卷 / 11期

关键词：

MUTATIONS; THROMBOCYTOPENIA; TRANSFORMATION; HEMATOPOIESIS; GENE;

D O I：

10.1002/ajh.26321

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Germline predisposition syndromes (GPS) result from constitutional aberrations in tumor suppressive and homeostatic genes, increasing risk for neoplasia in affected kindred. In this study, we present clinical and genomic data on 144 Mayo Clinic patients with GPS; 59 evaluated prospectively using an algorithm-based diagnostic approach in the setting of a dedicated GPS/ inherited bone marrow failure syndrome (IBMFS) clinic. Seventy-two (50%) patients had IBMFS (telomere biology disorders-32,Fanconi anemia-18, Diamond Blackfan Anemia - 11, congenital neutropenia-5, Schwachman-Diamond Syndrome-5 and Bloom Syndrome-1), 27 (19%) had GPS with antecedent thrombocytopenia (RUNX1-FPD-15, ANKRD26-6, ETV6-2, GATA1-1, MPL-3), 28 (19%) had GPS without antecedent thrombocytopenia (GATA2 haploinsufficiency-16, DDX41-10, CBL-1 and CEBPA-1) and 17 (12%) had general cancer predisposition syndromes (ataxia telangiectasia-7, heterozygous ATM variants-3, CHEK2-2, TP53-2, CDK2NA-1, NF1-1 and Nijmegen Breakage Syndrome-1). Homozygous and heterozygous ATM pathogenic variants were exclusively associated with lymphoproliferative disorders (LPD), while DDX41 GPS was associated with LPD and myeloid neoplasms. The use of somatic NGS-testing identified clonal evolution in GPS patients, with ASXL1, RAS pathway genes, SRSF2 and TET2 being most frequently mutated. Fifty-two (91%) of 59 prospectively identified GPS patients had a change in their management approach, including additional GPS-related screening in 42 (71%), referral for allogenic HSCT workup and screening of related donors in 16 (27%), medication initiation and selection of specific conditioning regimens in 14 (24%), and genetic counseling with specific intent of fertility preservation and preconceptual counseling in 10 (17%) patients; highlighting the importance of dedicated GPS screening, detection and management programs for patients with hematological neoplasms.

引用

页码：1450 / 1460

页数：11

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