TY - JOUR
T1 - Exome sequencing reveals recurrent germ line variants in patients with familial Waldenström macroglobulinemia
AU - Roccaro, Aldo M.
AU - Sacco, Antonio
AU - Shi, Jiantao
AU - Chiarini, Marco
AU - Perilla-Glen, Adriana
AU - Manier, Salomon
AU - Glavey, Siobhan
AU - Aljawai, Yosra
AU - Mishima, Yuji
AU - Kawano, Yawara
AU - Moschetta, Michele
AU - Correll, Mick
AU - Improgo, Ma Reina
AU - Brown, Jennifer R.
AU - Imberti, Luisa
AU - Rossi, Giuseppe
AU - Castillo, Jorge J.
AU - Treon, Steven P.
AU - Freedman, Matthew L.
AU - Van Allen, Eliezer M.
AU - Hide, Winston
AU - Hiller, Elaine
AU - Rainville, Irene
AU - Ghobrial, Irene M.
N1 - Publisher Copyright:
© 2016 by The American Society of Hematology.
PY - 2016/5/26
Y1 - 2016/5/26
N2 - Familial aggregation of Waldenström macroglobulinemia (WM) cases, and the clustering of B-cell lymphoproliferative disorders among first-degree relatives of WM patients, has been reported. Nevertheless, the possible contribution of inherited susceptibility to familial WM remains unrevealed. We performed whole exome sequencing on germ line DNA obtained from 4 family members in which coinheritance for WM was documented in 3 of them, and screened additional independent 246 cases by using gene-specific mutation sequencing. Among the shared germ line variants, LAPTM5c403t and HCLS1g496a were the most recurrent, being present in 3/3 affected members of the index family, detected in 8% of the unrelated familial cases, and present in 0.5% of the nonfamilial cases and in <0.05 of a control population. LAPTM5 and HCLS1 appeared as relevant WM candidate genes that characterized familial WM individuals and were also functionally relevant to the tumor clone. These findings highlight potentially novel contributors for the genetic predisposition to familial WM and indicate that LAPTM5c403t and HCLS1g496a may represent predisposition alleles in patients with familial WM.
AB - Familial aggregation of Waldenström macroglobulinemia (WM) cases, and the clustering of B-cell lymphoproliferative disorders among first-degree relatives of WM patients, has been reported. Nevertheless, the possible contribution of inherited susceptibility to familial WM remains unrevealed. We performed whole exome sequencing on germ line DNA obtained from 4 family members in which coinheritance for WM was documented in 3 of them, and screened additional independent 246 cases by using gene-specific mutation sequencing. Among the shared germ line variants, LAPTM5c403t and HCLS1g496a were the most recurrent, being present in 3/3 affected members of the index family, detected in 8% of the unrelated familial cases, and present in 0.5% of the nonfamilial cases and in <0.05 of a control population. LAPTM5 and HCLS1 appeared as relevant WM candidate genes that characterized familial WM individuals and were also functionally relevant to the tumor clone. These findings highlight potentially novel contributors for the genetic predisposition to familial WM and indicate that LAPTM5c403t and HCLS1g496a may represent predisposition alleles in patients with familial WM.
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U2 - 10.1182/blood-2015-11-680199
DO - 10.1182/blood-2015-11-680199
M3 - Article
C2 - 26903547
AN - SCOPUS:84974621496
SN - 0006-4971
VL - 127
SP - 2598
EP - 2606
JO - Blood
JF - Blood
IS - 21
ER -