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Inter‐ and intra‐patient clonal and subclonal heterogeneity of chronic lymphocytic leukaemia: evidences from circulating and lymph nodal compartments
Author(s) -
Del Giudice Ilaria,
Marinelli Marilisa,
Wang Jiguang,
Bonina Silvia,
Messina Monica,
Chiaretti Sabina,
Ilari Caterina,
Cafforio Luciana,
Raponi Sara,
Mauro Francesca R.,
Di Maio Valeria,
De Propris Maria S.,
Nanni Mauro,
Ciardullo Carmela,
Rossi Davide,
Gaidano Gianluca,
Guarini Anna,
Rabadan Raul,
Foà Robin
Publication year - 2016
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.13859
Subject(s) - somatic evolution in cancer , somatic cell , lymph , biology , compartment (ship) , mutation , exome sequencing , pathology , cancer research , microbiology and biotechnology , genetics , cancer , medicine , gene , oceanography , geology
Summary Whole exome sequencing and copy number aberration ( CNA ) analysis were performed on cells taken from peripheral blood ( PB ) and lymph nodes ( LN ) of patients with chronic lymphocytic leukaemia ( CLL ). Of 64 non‐silent somatic mutations, 54 (84·4%) were clonal in both compartments, 3 (4·7%) were PB ‐specific and 7 (10·9%) were LN ‐specific. Most of the LN ‐ or PB ‐specific mutations were subclonal in the other corresponding compartment (variant frequency 0·5–5·3%). Of 41 CNA s, 27 (65·8%) were shared by both compartments and 7 (17·1%) were LN ‐ or PB ‐specific. Overall, 6 of 9 cases (66·7%) showed genomic differences between the compartments. At subsequent relapse, Case 10, with 6 LN ‐specific lesions, and Case 100, with 6 LN ‐specific and 8 PB ‐specific lesions, showed, in the PB , the clonal expansion of LN ‐derived lesions with an adverse impact: SF 3B1 mutation, BIRC 3 deletion , del8(p23·3‐p11·1), del9(p24·3‐p13·1) and gain 2(p25·3‐p14). CLL shows an intra‐patient clonal heterogeneity according to the disease compartment, with both LN and PB ‐specific mutations/ CNA s. The LN microenvironment might contribute to the clonal selection of unfavourable lesions, as LN ‐derived mutations/ CNA s can appear in the PB at relapse.