Bailey Kelly M, Jacobs Michelle F, Anderson Bailey, Rabah Raja, Wu Yi-Mi, Else Tobias, Mody Rajen J
University of Pittsburgh School of Medicine, Pittsburgh, PA.
Michigan Medicine, Ann Arbor, MI.
JCO Precis Oncol. 2019;3. doi: 10.1200/po.18.00172. Epub 2019 Mar 11.
syndrome is a recently described inherited cancer predisposition syndrome caused by pathogenic variants in . With the recent increase in integrative clinical sequencing for pediatric patients with cancer, our understanding of the syndrome continues to evolve, as new and rare pathogenic variants are reported. As the frequency of integrative clinical sequencing increases, discussions regarding challenges encountered in the interpretation of sequencing results are essential to continue to advance the field of cancer predisposition. The purpose of this work was to identify patients with somatic and/or germline variants in our patient population and to discuss sequencing interpretation and the clinical recommendations that result from the integrative clinical sequencing results.
Patients were enrolled in the PEDS-MIONCOSEQ study. This integrative clinical sequencing study includes paired tumor/normal whole-exome sequencing and tumor transcriptome sequencing. Patients identified as having variants were included.
We report a variant of unknown clinical significance in a patient with a highly unusual response to therapy. Two patients had diagnoses clarified once the integrative clinical sequencing revealing a variant was available. We also discovered a patient with low-level mosaicism and the challenges encountered in the sequencing interpretation for this patient. In addition to the sequencing data and result interpretation, this work also highlights testing and screening recommendations made to patients with variants and their families on the basis of these results.
This work serves to extend the phenotype and advance the utility of clinical integrative sequencing in the fields of pediatric oncology and cancer genetic predisposition.
[综合征名称]是一种最近被描述的遗传性癌症易感性综合征，由[相关基因名称]中的致病变异引起。随着近期针对儿科癌症患者的综合临床测序的增加，随着新的和罕见的致病变异被报道，我们对[综合征名称]综合征的理解不断发展。随着综合临床测序频率的增加，讨论测序结果解释中遇到的挑战对于继续推动癌症易感性领域的发展至关重要。这项工作的目的是在我们的患者群体中识别出具有体细胞和/或种系[相关基因名称]变异的患者，并讨论测序解释以及综合临床测序结果所产生的临床建议。
患者被纳入PEDS - MIONCOSEQ研究。这项综合临床测序研究包括配对的肿瘤/正常全外显子测序和肿瘤转录组测序。纳入被鉴定为具有[相关基因名称]变异的患者。
我们报告了一名对治疗反应异常的患者中一个临床意义未知的[相关基因名称]变异。一旦综合临床测序揭示出[相关基因名称]变异，两名患者的诊断得以明确。我们还发现了一名低水平[相关基因名称]嵌合体患者以及对此患者测序解释中遇到的挑战。除了测序数据和结果解释外，这项工作还强调了根据这些结果向具有[相关基因名称]变异的患者及其家属提出的检测和筛查建议。
这项工作有助于扩展[综合征名称]的表型，并提高临床综合测序在儿科肿瘤学和癌症遗传易感性领域的效用。
