The Identification of Large Rearrangements Involving Intron 2 of the CDH1 Gene in BRCA1/2 Negative and Breast Cancer Susceptibility
Abstract
:1. Introduction
2. Material and Methods
2.1. Patients and Data Collection
2.2. DNA and RNA Preparations
2.3. Zoom-in CGH-Array
2.4. Breakpoint Sequencing
2.5. qPCR-HRM
2.6. RNA Analysis
2.7. Immunochemistry
2.8. Nomenclature
2.9. Statical Analysis
3. Results
4. Discussion
N | Rearrangements | Rearrangement Coordinates (hg18/GRCh36) | Gain/Loss | Reported Frequency | Size (bp) | Start# | End# | Classification | Reference |
---|---|---|---|---|---|---|---|---|---|
1 | Exon 3 deletion | chr16: 67,387,135–67,394,109 | Loss | 1/148 | 6975 | Intron 2 AluSx | Intron 3 AluSx | Deleterious c.164-5939_387+812del, p.Val55GlyfsX38 | This study and [29] |
2 | Full CDH3 sequence and CDH1 exon 1–2 deletion | chr16: 67,193,822–67,387,415 | Loss | 2/93 | 193,594 | 5′ region AluSp | Intron 2 AluSg | Deleterious c.-124-u134874_164-5659del, p. | [23] |
3 | Exon 1–2 deletion | chr16: 67,324,886–67,330,557 | Loss | 1/93 | 5672 | 5′ region AluSx | Intron 2 AluSg | Deleterious c.-124-u3810_163+742del, p. | [23,37] |
4 | Intron 2 deletion | chr16: 67,358,862–67,362,674 | Loss | 1/148 | 3811 | Intron 2 AluSx | Intron 2 AluJo | CNV | This study |
5 | Intron 2 duplication | chr16: 67,345,633–67,350,721 | Gain | 1/148 | 5089 | Intron 2 AluJo | Intron 2 FLAM_C | CNV | This study |
6 | Intron 2 CNV 67021 | chr16: 67,345,074–67,351,437 | Gain | 24/450 | 6364 | Intron 2 | Intron 2 | CNV | [38] |
7 | Intron 2 CNV 77387 | chr16: 67,345,117–67,348,065 | Gain | 9/90 | 2949 | Intron 2 MER-53 | Intron 2 | CNV | [39] |
8 | Intron 2 CNV 88182 | chr16: 67,347,663–67,348,065 | Loss | 1/90 | 403 | Intron 2 | Intron 2 | CNV | [39] |
9 | Intron 2 CNV 5831 | chr16: 67,330,369–67,331,573 | Loss | 1/36 | 1205 | Intron 2 AluJo | Intron 2 | CNV | [40] |
10 | Exon 1 deletion | chr16: 67,328,695–67,328,844 | Loss | 1/93 | 150 | AluJo | Intron 1 AluJo | Deleterious | [23] |
11 | Exon 14–16 deletion | chr16: 67,416,845–67,424,923 | Loss | 1/93 | 8078 | FLAM_C Intron 13 | 3′ region AluJb | Deleterious | [23] |
12 | Exon 16 deletion | chr16: 67,424,298–67,425,126 | Loss | 1/93 | 828 | AluSq Intron 15 | 3′ region AluJb | Deleterious | [23,37] |
13 | Exon 4–16 duplication CNV 77388 | chr16: 67,397,988–67,426,849 | Gain | 1/90 | 28,862 | Intron 3 MIR | 3′ region | Deleterious c.388-1840_*1946del, p.Ala130MetfsX155 | [39] |
14 | Exon 13–14 duplication CNV 9761 | chr16: 67,414,790–67,420,815 | Gain | 1/112 | 6026 | Intron 13 | Intron 14 | Deleterious c.1937-13_2296-243del p.Gln647ValfsX10 | [41] |
15 | Intron 15 CNV 67022 | chr16: 67,421,302–67,424,310 | Loss | 5/450 | 3009 | Intron 15 | Intron 15 | CNV | [38] |
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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Gene | CDH1 | |||
---|---|---|---|---|
Exon/Intron | Exon n°3 | Intron n°2 | ||
Zoom in gene region (hg18/GRCh36) | chr16: 67,387,135–67,394,109 | chr16: 67,358,862–67,362,674 | chr16: 67,345,633–67,350,721 | |
Type of rearrangement | Heterozygous deletion of 6975 pb | Heterozygous deletion of 3812 bp | Heterozygous duplication of 5089 bp | |
c. position | c.164-5939_387+812del | c.163+29048_164-30362del | c.163+15818_163+20906dup | |
Clinicopathogical characteristicsof the patient | Age at diagnosis | 32 | 58 | 49 |
Personal history | Bilateral lobular BC and metachronous diffuse gastric carcinoma. | Ductal Invasive BC | A mix of lobular and ductal In situ carcinomas. | |
Familial history | No history | BC/CRC | BC | |
E-Cadherin expression | Homogeneous loss (Figure 5A) | Heterogeneous loss | Heterogeneous loss (Figure 5B) | |
Protein change | p.Val55Glyfs*38 | - | - | |
Classification | Deleterious | CNV | CNV |
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Share and Cite
Ben Aissa-Haj, J.; Pinheiro, H.; Cornelis, F.; Sebai, M.; Meseure, D.; Briaux, A.; Berteaux, P.; Lefol, C.; Des Guetz, G.; Trassard, M.; Stevens, D.; Vialard, F.; Bieche, I.; Noguès, C.; Tang, R.; Oliveira, C.; Stoppat-Lyonnet, D.; Lidereau, R.; Rouleau, E. The Identification of Large Rearrangements Involving Intron 2 of the CDH1 Gene in BRCA1/2 Negative and Breast Cancer Susceptibility. Genes 2022, 13, 2213. https://doi.org/10.3390/genes13122213
Ben Aissa-Haj J, Pinheiro H, Cornelis F, Sebai M, Meseure D, Briaux A, Berteaux P, Lefol C, Des Guetz G, Trassard M, Stevens D, Vialard F, Bieche I, Noguès C, Tang R, Oliveira C, Stoppat-Lyonnet D, Lidereau R, Rouleau E. The Identification of Large Rearrangements Involving Intron 2 of the CDH1 Gene in BRCA1/2 Negative and Breast Cancer Susceptibility. Genes. 2022; 13(12):2213. https://doi.org/10.3390/genes13122213
Chicago/Turabian StyleBen Aissa-Haj, Jihenne, Hugo Pinheiro, François Cornelis, Molka Sebai, Didier Meseure, Adrien Briaux, Philippe Berteaux, Cedric Lefol, Gaëtan Des Guetz, Martine Trassard, Denise Stevens, François Vialard, Ivan Bieche, Catherine Noguès, Roseline Tang, Carla Oliveira, Dominique Stoppat-Lyonnet, Rosette Lidereau, and Etienne Rouleau. 2022. "The Identification of Large Rearrangements Involving Intron 2 of the CDH1 Gene in BRCA1/2 Negative and Breast Cancer Susceptibility" Genes 13, no. 12: 2213. https://doi.org/10.3390/genes13122213