The frequent and clinically benign anomalies of chromosomes 7 and 20 in Shwachman-diamond syndrome may be subject to further clonal variations

Abstract Background An isochromosome of the long arm of chromosome 7, i(7)(q10), and an interstitial deletion of the long arm of chromosome 20, del(20)(q), are the most frequent anomalies in the bone marrow of patients with Shwachman-Diamond syndrome, which is caused in most cases by mutations of th...

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Autores principales:	Abdul Waheed Khan, Alyssa Kennedy, Elissa Furutani, Kasiani Myers, Annalisa Frattini, Francesco Acquati, Pamela Roccia, Giovanni Micheloni, Antonella Minelli, Giovanni Porta, Marco Cipolli, Simone Cesaro, Cesare Danesino, Francesco Pasquali, Akiko Shimamura, Roberto Valli
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Bone marrow rescue Chromosome anomalies Karyotype instability Shwachman-Diamond syndrome Genetics QH426-470
Acceso en línea:	https://doaj.org/article/3fc874865da740418e5b38c9fe52d387
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spelling	oai:doaj.org-article:3fc874865da740418e5b38c9fe52d3872021-11-28T12:04:47ZThe frequent and clinically benign anomalies of chromosomes 7 and 20 in Shwachman-diamond syndrome may be subject to further clonal variations10.1186/s13039-021-00575-w1755-8166https://doaj.org/article/3fc874865da740418e5b38c9fe52d3872021-11-01T00:00:00Zhttps://doi.org/10.1186/s13039-021-00575-whttps://doaj.org/toc/1755-8166Abstract Background An isochromosome of the long arm of chromosome 7, i(7)(q10), and an interstitial deletion of the long arm of chromosome 20, del(20)(q), are the most frequent anomalies in the bone marrow of patients with Shwachman-Diamond syndrome, which is caused in most cases by mutations of the SBDS gene. These clonal changes imply milder haematological symptoms and lower risk of myelodysplastic syndromes and acute myeloid leukaemia, thanks to already postulated rescue mechanisms. Results Bone marrow from fourteen patients exhibiting either the i(7)(q10) or the del(20)(q) and coming from two large cohorts of patients, were subjected to chromosome analyses, Fluorescent In Situ Hybridization with informative probes and array-Comparative Genomic Hybridization. One patient with the i(7)(q10) showed a subsequent clonal rearrangement of the normal chromosome 7 across years. Four patients carrying the del(20)(q) evolved further different del(20)(q) independent clones, within a single bone marrow sample, or across sequential samples. One patient with the del(20)(q), developed a parallel different clone with a duplication of chromosome 3 long arm. Eight patients bore the del(20)(q) as the sole chromosomal abnormality. An overall overview of patients with the del(20)(q), also including cases already reported, confirmed that all the deletions were interstitial. The loss of material varied from 1.7 to 26.9 Mb and resulted in the loss of the EIF6 gene in all patients. Conclusions Although the i(7)(q) and the del(20)(q) clones are frequent and clinically benign in Shwachman Diamond-syndrome, in the present work we show that they may rearrange, may be lost and then reconstructed de novo, or may evolve with independent clones across years. These findings unravel a striking selective pressure exerted by SBDS deficiency driving to karyotype instability and to specific clonal abnormalities.Abdul Waheed KhanAlyssa KennedyElissa FurutaniKasiani MyersAnnalisa FrattiniFrancesco AcquatiPamela RocciaGiovanni MicheloniAntonella MinelliGiovanni PortaMarco CipolliSimone CesaroCesare DanesinoFrancesco PasqualiAkiko ShimamuraRoberto ValliBMCarticleBone marrow rescueChromosome anomaliesKaryotype instabilityShwachman-Diamond syndromeGeneticsQH426-470ENMolecular Cytogenetics, Vol 14, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Bone marrow rescue Chromosome anomalies Karyotype instability Shwachman-Diamond syndrome Genetics QH426-470
spellingShingle	Bone marrow rescue Chromosome anomalies Karyotype instability Shwachman-Diamond syndrome Genetics QH426-470 Abdul Waheed Khan Alyssa Kennedy Elissa Furutani Kasiani Myers Annalisa Frattini Francesco Acquati Pamela Roccia Giovanni Micheloni Antonella Minelli Giovanni Porta Marco Cipolli Simone Cesaro Cesare Danesino Francesco Pasquali Akiko Shimamura Roberto Valli The frequent and clinically benign anomalies of chromosomes 7 and 20 in Shwachman-diamond syndrome may be subject to further clonal variations
description	Abstract Background An isochromosome of the long arm of chromosome 7, i(7)(q10), and an interstitial deletion of the long arm of chromosome 20, del(20)(q), are the most frequent anomalies in the bone marrow of patients with Shwachman-Diamond syndrome, which is caused in most cases by mutations of the SBDS gene. These clonal changes imply milder haematological symptoms and lower risk of myelodysplastic syndromes and acute myeloid leukaemia, thanks to already postulated rescue mechanisms. Results Bone marrow from fourteen patients exhibiting either the i(7)(q10) or the del(20)(q) and coming from two large cohorts of patients, were subjected to chromosome analyses, Fluorescent In Situ Hybridization with informative probes and array-Comparative Genomic Hybridization. One patient with the i(7)(q10) showed a subsequent clonal rearrangement of the normal chromosome 7 across years. Four patients carrying the del(20)(q) evolved further different del(20)(q) independent clones, within a single bone marrow sample, or across sequential samples. One patient with the del(20)(q), developed a parallel different clone with a duplication of chromosome 3 long arm. Eight patients bore the del(20)(q) as the sole chromosomal abnormality. An overall overview of patients with the del(20)(q), also including cases already reported, confirmed that all the deletions were interstitial. The loss of material varied from 1.7 to 26.9 Mb and resulted in the loss of the EIF6 gene in all patients. Conclusions Although the i(7)(q) and the del(20)(q) clones are frequent and clinically benign in Shwachman Diamond-syndrome, in the present work we show that they may rearrange, may be lost and then reconstructed de novo, or may evolve with independent clones across years. These findings unravel a striking selective pressure exerted by SBDS deficiency driving to karyotype instability and to specific clonal abnormalities.
format	article
author	Abdul Waheed Khan Alyssa Kennedy Elissa Furutani Kasiani Myers Annalisa Frattini Francesco Acquati Pamela Roccia Giovanni Micheloni Antonella Minelli Giovanni Porta Marco Cipolli Simone Cesaro Cesare Danesino Francesco Pasquali Akiko Shimamura Roberto Valli
author_facet	Abdul Waheed Khan Alyssa Kennedy Elissa Furutani Kasiani Myers Annalisa Frattini Francesco Acquati Pamela Roccia Giovanni Micheloni Antonella Minelli Giovanni Porta Marco Cipolli Simone Cesaro Cesare Danesino Francesco Pasquali Akiko Shimamura Roberto Valli
author_sort	Abdul Waheed Khan
title	The frequent and clinically benign anomalies of chromosomes 7 and 20 in Shwachman-diamond syndrome may be subject to further clonal variations
title_short	The frequent and clinically benign anomalies of chromosomes 7 and 20 in Shwachman-diamond syndrome may be subject to further clonal variations
title_full	The frequent and clinically benign anomalies of chromosomes 7 and 20 in Shwachman-diamond syndrome may be subject to further clonal variations
title_fullStr	The frequent and clinically benign anomalies of chromosomes 7 and 20 in Shwachman-diamond syndrome may be subject to further clonal variations
title_full_unstemmed	The frequent and clinically benign anomalies of chromosomes 7 and 20 in Shwachman-diamond syndrome may be subject to further clonal variations
title_sort	frequent and clinically benign anomalies of chromosomes 7 and 20 in shwachman-diamond syndrome may be subject to further clonal variations
publisher	BMC
publishDate	2021
url	https://doaj.org/article/3fc874865da740418e5b38c9fe52d387
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The frequent and clinically benign anomalies of chromosomes 7 and 20 in Shwachman-diamond syndrome may be subject to further clonal variations

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