case_images: PMC8190481_01
case_images: Allelic imbalance of chromosome 1q was observed in three of the four mantle cell lymphoma cases: in two at relapse in the central nervous system (patient 1 and 3, cerebrospinal fluid (CSF)) and one at diagnosis (patient 2). Each individual plot displays the allele frequencies of heterozygous variants (VAF) on chromosome 1 and significant deviation, or imbalance, from normal disomy. In all three cases, the aberration spanned almost 100 megabases distal to the centromere, and thus the majority of the q-arm. Sequencing of patient 2 CSF relapse material failed and thus could not be evaluated (*). All three evident allelic imbalances on the q-arm were significantly different from the p-arm (***, Wilcoxon rank-sum test:p <= 10-4, Kolmogorov-Smirnov test of equal distributions: p <= 10-4).
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case_images: A high burden deletion (~80%) was found at relapse on chromosome 1q (approximately 95 Mb, Fig. 1, patient 1 panel D, and Fig. 2) by whole-exome sequencing (WES). In addition, a distal 1q deletion of approximately 100 Mb was detected utilizing VAF and read depth ratio analyses of tumor-control pair (Fig. 1, patient 2, panel A), with an estimated cell fraction of 25-30%. This patient also displayed a large allelic imbalance (Fig. 1, patient 3, panel C) of 95-100 Mb at the same location as patients 1 and 2 (Fig. 2), however showing evidence of a chromosome copy-gain (Fig. 3, patient 3).
case_images: The size of the allelic imbalance on chromosome 1q was found to be approximately 100 megabases distal to the centromere across the three patients with apparent copy-alterations (the gradient marks the approximate starting point of the lesion of the four patients, as it is not possible to conclude the exact position from the whole-exome sequencing resolution).
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case_images: In addition, a distal 1q deletion of approximately 100 Mb was detected utilizing VAF and read depth ratio analyses of tumor-control pair (Fig. 1, patient 2, panel A), with an estimated cell fraction of 25-30%.
case_images: Coverage of the chromosome 1 q-arm region afflicted by allelic imbalance relative to the unaffected p-arm. Chromosome 1q of patient (pt.) 1 and 2 were evident of a copy-loss (A, dark gray), while a copy-gain was indicated for patient 3 (dark gray). All read depth ratios were normalized to that of the respective paired control. Samples without statistically significant allelic imbalance on the q-arm (white) were in close agreement with the paired control samples. BM: bone marrow, LN: lymph node, CSF: cerebrospinal fluid, PF: pleura fluid, DT: Dorsal tumor. The chromosome 1q imbalance observed in patient 1, 2 and, 3 were supported by qPCR (TaqMan Copy Number Assay) targeting the ABL2 gene (chromosome 1q25.2) and the reference gene TERT (chromosome 5p15.33).
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case_images: This patient also displayed a large allelic imbalance (Fig. 1, patient 3, panel C) of 95-100 Mb at the same location as patients 1 and 2 (Fig. 2), however showing evidence of a chromosome copy-gain (Fig. 3, patient 3).
case_images: Fundoscopy showing infiltration of malignant cells in corpus vitreum at relapse (left and right eye). Patient 4 experienced a CNS relapse without cerebrospinal clonal B cells. The patient was still alive after 60 months, and the malignant cells did not show any aberrations on chromosome 1 in contrast to the other cases.
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case_images: Assessment of the infiltration of corpus vitreum by fundoscopy confirmed the CNS relapse (Fig. 4), while no malignant cells were present in the CSF.