Journal Article

Clonal Hematopoiesis and Blood-Cancer Risk Inferred from Blood DNA Sequence

Lehmann, Sören, Handsaker, Robert E, Mick, Eran, Purcell, Shaun M, Kähler, Anna K, Svantesson, Oscar, Moran, Jennifer L, Lindberg, Johan, Chambert, Kimberly, McCarroll, Steven A, Bakhoum, Samuel F, Lander, Eric S, Sullivan, Patrick F, Gabriel, Stacey B, Genovese, Giulio, Rose, Samuel A, Fromer, Menachem, Grönberg, Henrik, Hultman, Christina M, Neale, Benjamin M, Sklar, Pamela, Landén, Mikael, Höglund, Martin

2014

Overview

In this study, clonal hematopoiesis with somatic mutations was found in 10% of otherwise healthy people older than 65. The risk of hematologic cancer was substantially increased among these persons; in two cases, the subsequent cancer was related to the clone that predated the cancer. The development of disease often involves dynamic processes that begin years or decades before the clinical onset. In many cases, however, the process of pathogenesis goes undetected until after the patient has symptoms and presents with clinically apparent disease. Cancer arises owing to the combined effects of multiple somatic mutations, which are likely to be acquired at different times. 1 Early mutations may be present many years before disease develops. In some models of cancer development, early mutations lead to clonal expansions by stem cells or other progenitor cells. 2 Such clonal expansions greatly increase the likelihood that later, cooperating mutations would . . .

• Publisher: Massachusetts Medical Society
• Subject: Acute myeloid leukemia / Adult / Age / Age Factors / Aged / Aged, 80 and over / Biological and medical sciences / Biopsy / Blood / Blood cancer / Blood cells / Blood diseases / Bone cancer / Bone marrow / Cancer / Cell differentiation, maturation, development, hematopoiesis / Cell physiology / Cell Transformation, Neoplastic - genetics / Clone Cells / Data processing / Deoxyribonucleic acid / Diagnosis / DNA / DNA Mutational Analysis / DNA sequencing / Exome / Fundamental and applied biological sciences. Psychology / General aspects / Genomes / Hematologic Neoplasms - genetics / Hematologic Neoplasms - physiopathology / Hematopoiesis - physiology / Hematopoietic Stem Cells - physiology / Humans / Medical sciences / Middle Aged / Molecular and cellular biology / Multiple tumors. Solid tumors. Tumors in childhood (general aspects) / Mutation / Myeloid leukemia / Nucleotide sequence / Pathogenesis / Peripheral blood / Phenotypes / Psychiatry / Psykiatri / Risk Factors / Sampling / Stem cells / Tumors / Young Adult