Department of Laboratory Medicine, University of California San Francisco, San Francisco, California, USA,
Department of Pathology, University of California San Francisco, San Francisco, California, USA.
Cytogenet Genome Res. 2022;162(3):119-123. doi: 10.1159/000525010. Epub 2022 Jun 8.
Interstitial deletion in the long arm of chromosome 9 [del(9q)] is a fairly common cytogenetic finding associated with acute myeloid leukemia (AML), seen in approximately 2-5% of AML patients. However, the genomic features of the deletion remain largely unknown. Using chromosome analysis, single nucleotide polymorphism microarray, and next-generation sequencing, we characterized del(9q)s and other genomic alterations in 9 AML patients. We found several distinct features of the del(9q)s. The proximal breakpoints of the deletions are clustered within a 2.5-Mb region (chr9: 68,513,625-70,984,372; GRCh37) enriched with segmental duplications, which may represent a "hotspot" for genomic rearrangements. However, the distal breakpoints of the deletions vary significantly. In addition, the overall deleted region could be divided into a 14.4-Mb proximal constitutional region (chr9: 70,950,015-85,397,699; 9q21.11q21.32) and a 24.0-Mb distal oncogenic region (chr9: 85,397,700-109,427,261; 9q21.32q31.1). We further identified a 6.8-Mb common overlapped deletion region (CODR) in the distal region (chr9: 90,590,650-97,366,400). This CODR carries multiple genes that are reportedly involved in cancer pathogenesis. The prognostic value of the del(9q) in AML apparently depends on additional genomic alterations in the patients.
9 号染色体长臂的杂合性缺失(del(9q))是一种常见的细胞遗传学异常,与急性髓细胞白血病(AML)相关,约见于 2-5%的 AML 患者。然而,该缺失的基因组特征仍知之甚少。本研究通过染色体分析、单核苷酸多态性微阵列和下一代测序,对 9 例 AML 患者的 del(9q)及其他基因组改变进行了特征分析。我们发现 del(9q)存在一些独特的特征。缺失的近端断点集中在 2.5Mb 的区域(chr9: 68,513,625-70,984,372;GRCh37)内,该区域富含片段重复,这可能代表基因组重排的“热点”。然而,缺失的远端断点差异较大。此外,总的缺失区域可分为 14.4Mb 的近端同源性缺失区域(chr9: 70,950,015-85,397,699;9q21.11q21.32)和 24.0Mb 的远端致癌区域(chr9: 85,397,700-109,427,261;9q21.32q31.1)。我们进一步在远端区域(chr9: 90,590,650-97,366,400)鉴定出一个 6.8Mb 的共同缺失区域(CODR)。该 CODR 携带多个据报道与癌症发病机制相关的基因。del(9q)在 AML 中的预后价值显然取决于患者的其他基因组改变。