The profiles and somatic mutations of HLA-A allele–lacking granulocytes
| Case no. . | HLA-LLs . | SNP array . | Mutated genes . | |||||
|---|---|---|---|---|---|---|---|---|
| Lost allele . | Lineage combination pattern . | % in the total G population . | 6pLOH frequency in HLA−granulocytes, % . | CNV . | Targeted sequencing, n = 15 . | WES, n = 5 . | Median VAF . | |
| 1 | A24 | GM | 49.6 | 96 | NE | DNMT3A, ZRSR2, TET2 | NE | 0.36 |
| 2 | A31 | GMB | 99.7 | 36 (Discrepancy) | 6pLOH* | DNMT3A | NE | 0.19 |
| 3 | A2 | GMBT | 94.2 | 46† (Discrepancy) | 6pLOH* | LRCH1, PRR5L | NE | 0.11 |
| 4 | A31 | GMB | 99.0 | 99 | 6pLOH | CBL | NE | 0.33 |
| 5 | A2 | GMBT | 62.1 | 75† (Discrepancy) | 6pLOH | (−) | NE | — |
| 6 | A2 | GMBT | 5.5 | 70† (Discrepancy) | 6pLOH* | (−) | NE | — |
| 7 | A2 | GM | 6.4 | 92 | 6pLOH | (−) | NE | — |
| 8 | A2 | GMB | 9.8 | 96 | 6pLOH | (−) | NE | — |
| 9 | A24 | GMBT | 40.9 | 99 | 6pLOH | (−) | NE | — |
| 10 | A31 | GMBT | 98.6 | 33 (Discrepancy) | 6pLOH | (−) | NE | — |
| 11 | A24 | GMB | 25.1 | 92† | 6pLOH | (−) | (−) | — |
| 12 | A2 | GMBT | 97.7 | 92† | 6pLOH* | (−) | 11 genes (PPAP2B, MYSM1, FER1L5, SP5, OR2AT4, PEX5, FAM154B, SRRM2, GPR56, NLRP4, COX4I2) | 0.45 |
| 13 | A2 | GMBT | 99.8 | 99 | 6pLOH | (−)‡ | 2 genes (ZNF502, DHX35) | 0.49 |
| 14 | A2 | GMBT | 98.6 | 99 | 6pLOH | (−)‡ | 5 genes (GPT, ZNF462, CTCRTA1, OLFM4, SERPINF1) | 0.22 |
| 15 | A31 | GMB | 98.6 | 99 | 6pLOH | (−) | 3 genes (EDEM3, ATXN1L, AKAP10), 11pLOH | 0.44 |
| Case no. . | HLA-LLs . | SNP array . | Mutated genes . | |||||
|---|---|---|---|---|---|---|---|---|
| Lost allele . | Lineage combination pattern . | % in the total G population . | 6pLOH frequency in HLA−granulocytes, % . | CNV . | Targeted sequencing, n = 15 . | WES, n = 5 . | Median VAF . | |
| 1 | A24 | GM | 49.6 | 96 | NE | DNMT3A, ZRSR2, TET2 | NE | 0.36 |
| 2 | A31 | GMB | 99.7 | 36 (Discrepancy) | 6pLOH* | DNMT3A | NE | 0.19 |
| 3 | A2 | GMBT | 94.2 | 46† (Discrepancy) | 6pLOH* | LRCH1, PRR5L | NE | 0.11 |
| 4 | A31 | GMB | 99.0 | 99 | 6pLOH | CBL | NE | 0.33 |
| 5 | A2 | GMBT | 62.1 | 75† (Discrepancy) | 6pLOH | (−) | NE | — |
| 6 | A2 | GMBT | 5.5 | 70† (Discrepancy) | 6pLOH* | (−) | NE | — |
| 7 | A2 | GM | 6.4 | 92 | 6pLOH | (−) | NE | — |
| 8 | A2 | GMB | 9.8 | 96 | 6pLOH | (−) | NE | — |
| 9 | A24 | GMBT | 40.9 | 99 | 6pLOH | (−) | NE | — |
| 10 | A31 | GMBT | 98.6 | 33 (Discrepancy) | 6pLOH | (−) | NE | — |
| 11 | A24 | GMB | 25.1 | 92† | 6pLOH | (−) | (−) | — |
| 12 | A2 | GMBT | 97.7 | 92† | 6pLOH* | (−) | 11 genes (PPAP2B, MYSM1, FER1L5, SP5, OR2AT4, PEX5, FAM154B, SRRM2, GPR56, NLRP4, COX4I2) | 0.45 |
| 13 | A2 | GMBT | 99.8 | 99 | 6pLOH | (−)‡ | 2 genes (ZNF502, DHX35) | 0.49 |
| 14 | A2 | GMBT | 98.6 | 99 | 6pLOH | (−)‡ | 5 genes (GPT, ZNF462, CTCRTA1, OLFM4, SERPINF1) | 0.22 |
| 15 | A31 | GMB | 98.6 | 99 | 6pLOH | (−) | 3 genes (EDEM3, ATXN1L, AKAP10), 11pLOH | 0.44 |
“(Discrepancy)” indicates the presence of a discrepancy in the percentage between 6pLOH+ cells and HLA-LLs. —, not calculated; (−), not detected;
6pLOH, copy-number neutral loss of heterozygosity in chromosome 6p; CNV, copy-number variant; GM, granulocytes, monocytes; GMB, granulocytes, monocytes, B cells; GMBT, granulocytes, monocytes, B cells, and T cells; NE, not evaluated; SNP, single-nucleotide polymorphism; VAF, variant allele frequency; WES, whole-exome sequencing.
Breakpoints of 6pLOH resided between the HLA-A and -C alleles were revealed by HLA-allelic sequencing.
6pLOH frequencies were estimated by HLA sequencing.
Previous targeted sequencing failed to reveal any mutations in 106 genes, most of which are known to be recurrently mutated in myeloid malignancies.7