Deletion at chromosome arms 6q16–22 and 10q22.3–23.1 associated with initiation of prostate cancer

Abstract

Loss of heterozygosity (LOH) at 6q16-22 and 10q22.3-23.1 is common chromosomal alteration in advanced prostate cancer and suggests that one or more tumor suppressor genes may lie within these chromosome arms. However, the genetic changes in early stage prostate cancer and premalignant lesions remain to be investigated. We used 11 informative microsatellite markers at 6q16-22 and 10q22.3-23.1 in Japanese patients to compare the frequency of LOH in 53 lesions of high-grade prostatic intraepithelial neoplasia (HGPIN), 38 cases (38 lesions) of incidental prostate cancer (IPC) and 107 cases (168 lesions) of clinical prostate cancer (CPC). The frequency of LOH at 6q16-22 with at least one marker was 38 and 49% in IPC and CPC cases, respectively. Similarly, allelic loss at 10q22.3-23.1 was present in 35 and 39% of IPC and CPC, respectively. High-frequency LOH was detected in both the clinically insignificant and significant prostate cancers at 6q16-22 and 10q22.3-23.1 (P40.05). However, no allelic loss was detected in any markers at the same regions in HGPIN (0%), which is usually considered a premalignant lesion to prostate cancer. Deletions of both the chromosome regions, 6q16-22 and 10q22.3-23.1, are more likely important events in the initiation and/or promotion of prostate cancer.

FANCJ is essential to maintain microsatellite structure genome-wide during replication stress

“…8q24.21, leukemia/lymphoma (66,67); chr. 10q22.3, non-small cell lung cancer, prostate cancer (68,69); chr. 11p.15.4-5, Beckwith-Wiedemann cancer predisposition syndrome, T lymphoid leukemia (70–72); chr.…”

CRISPR screens reveal genetic determinants of PARP inhibitor sensitivity and resistance in prostate cancer

“…Indeed, WDR76 has a large interaction network, including HELLS and PARP1 30 , supporting synthetically lethal interaction with PARP inhibition. RNASEH2B and MMS22L are located on chromosomes 13q14 and 6q16, respectively, which have long been recognized as two frequently deleted regions in PCa [31][32][33][34][35][36][37] . While loss of RNASEH2B might cause ribonucleotide excision repair deficiency and PARP-trapping lesions as previously reported 13 , we recently reported that co-loss of RB1, a closely located tumor suppressor gene, was antagonistic in PCa cells 38 .…”

CRISPR screens reveal genetic determinants of PARP inhibitor sensitivity and resistance in prostate cancer

“…RNASEH2B and MMS22L are located on chromosomes 13q14 and 6q16, respectively, which are two genomic regions frequently deleted in PCa [29][30][31][32][33][34][35] . While loss of RNASEH2B might cause ribonucleotide excision repair deficiency and PARP-trapping lesions as previously reported 13 , we recently reported that co-loss of RB1, a closely located tumor suppressor gene, was antagonistic in PCa cells 36 .…”