McKenna Danielle B, Van Den Akker Jeroen, Zhou Alicia Y, Ryan Lauren, Leon Annette, O'Connor Robert, Shah Payal D, Rustgi Anil K, Katona Bryson W
Division of Hematology-Oncology, Department of Medicine, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
Color Genomics, Burlingame, CA, 94010, USA.
Fam Cancer. 2019 Jan;18(1):63-66. doi: 10.1007/s10689-018-0090-6.
Hereditary mixed polyposis syndrome (HMPS) is a hereditary syndrome that is characterized by multiple colon polyps of mixed pathologic subtypes and an increased risk for colorectal cancer. A 40 kb duplication in the 5' regulatory region of the GREM1 gene was recently found to be the causal mutation in a subset of Ashkenazi Jewish families with HMPS. Given this discovery, the GREM1 5' regulatory region is now analyzed on many different multi-gene cancer panels, however the data on duplications distinct from the 40 kb duplication remains minimal. Herein we report a novel 24 kb tandem duplication of the 5' regulatory region of GREM1 in a patient without Ashkenazi Jewish heritage, who had a family history that was concerning for Lynch syndrome and satisfied Amsterdam II criteria. This is only the third reported GREM1 duplication separate from the 40 kb Ashkenazi Jewish duplication, and is the only reported duplication to selectively involve exon 1 of GREM1. This finding supports comprehensive testing of the GREM1 regulatory region in families of all ethnicities with multiple colon polyps or colon cancer, and when Lynch syndrome is suspected.
遗传性混合性息肉病综合征（HMPS）是一种遗传性综合征，其特征为具有多种病理亚型的多个结肠息肉以及患结直肠癌的风险增加。最近发现，GREM1基因5'调控区域的一个40 kb重复是一部分患有HMPS的阿什肯纳兹犹太人家族中的致病突变。鉴于这一发现，现在许多不同的多基因癌症检测板都对GREM1 5'调控区域进行分析，然而，与40 kb重复不同的重复数据仍然很少。在此，我们报告了一名没有阿什肯纳兹犹太血统的患者中GREM1基因5'调控区域的一个新的24 kb串联重复，该患者有家族性林奇综合征病史且符合阿姆斯特丹II标准。这是第三例报道的与40 kb阿什肯纳兹犹太重复不同的GREM1重复，也是唯一一例报道的选择性涉及GREM1外显子1的重复。这一发现支持对所有有多个结肠息肉或结肠癌且怀疑患有林奇综合征的不同种族家族进行GREM1调控区域的全面检测。
