SF3B1 and Other Novel Cancer Genes in Chronic Lymphocytic Leukemia

• Published in: The New England journal of medicine Vol. 365; no. 26; pp. 2497 - 2506
• Main Authors: Wang, Lili, Lawrence, Michael S, Wan, Youzhong, Stojanov, Petar, Sougnez, Carrie, Stevenson, Kristen, Werner, Lillian, Sivachenko, Andrey, DeLuca, David S, Zhang, Li, Zhang, Wandi, Vartanov, Alexander R, Fernandes, Stacey M, Goldstein, Natalie R, Folco, Eric G, Cibulskis, Kristian, Tesar, Bethany, Sievers, Quinlan L, Shefler, Erica, Gabriel, Stacey, Hacohen, Nir, Reed, Robin, Meyerson, Matthew, Golub, Todd R, Lander, Eric S, Neuberg, Donna, Brown, Jennifer R, Getz, Gad, Wu, Catherine J
• Format: Journal Article
• Language: English
• Published: Waltham, MA Massachusetts Medical Society 29-12-2011
• Subjects: Adult; Biological and medical sciences; Cancer; Cdc4 protein; Chromosome 11; Chromosome Deletion; Chromosomes; Chromosomes, Human, Pair 11 - genetics; Chronic lymphocytic leukemia; Deoxyribonucleic acid; DNA; DNA sequencing; DNA, Neoplasm - analysis; Exome - genetics; Gene Library; General aspects; Genetic testing; Genetics; Genomes; Hematologic and hematopoietic diseases; High-Throughput Nucleotide Sequencing; Humans; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell - genetics; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphatic leukemia; Medical sciences; Mortality; mRNA; Mutation; Mutation, Missense; MyD88 protein; Notch1 protein; p53 Protein; RNA Splicing; Spliceosomes - genetics; Splicing; Tumors; Medicine; Chronic lymphocytic leukemia; Gene; Lymphoproliferative syndrome; Genetics; Malignant hemopathy; Malignant tumor; Cancer
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa1109016

CLL is a heterogeneous disease with a variable clinical course and response to therapy. New genetic lesions have been noted in subgroups of patients through whole-exome and whole-genome sequencing. An abnormality in RNA splicing has been found in 15% of patients.
Chronic lymphocytic leukemia is an incurable disease characterized by extensive clinical heterogeneity despite a common diagnostic immunophenotype (surface expression of CD19+, CD20+dim, CD5+, CD23+, and sIgMdim). Whereas the course of disease is indolent in some patients, it is steadily progressive in approximately half of patients, leading to substantial morbidity and mortality.
1
Our ability to predict a more aggressive disease course has improved with the use of tests for biologic markers (degree of somatic hypermutation in the variable region of the immunoglobulin heavy chain [
IGHV
] gene and expression of ZAP70) and the detection of cytogenetic abnormalities (deletions . . .